Patients must have follicular lymphoma (grade I, II or IIIa) confirmed at initial diagnosis and at relapse with identifiable fludeoxyglucose F-18 (FDG) avid disease on PET/CT; patients that have involvement with large cell lymphoma are not eligible
Systemic lymphoma
Fluorodeoxyglucose (FDG)-avid lymphoma (that is [i.e.], PET-positive lymphoma)
Histologically confirmed, relapsed or refractory, follicular B-cell NHL (follicular lymphoma) Grade 1, 2, and 3a.
Subjects who have Burkitt's lymphoma or Burkitt-like lymphoma.
Grade 3b follicular lymphoma
One of the following untreated, histological confirmed lymphoma expressing cluster of differentiation (CD)20 antigen\r\n* DLBCL with disconcordant and/or composite pathology e.g. low grade follicular lymphoma within bone marrow or lymph node are eligible\r\n* DLBCL transformation follicular lymphoma (FL) – untreated with anthracyclines or high dose chemotherapy/autologous stem cell transplantation; patients treated with rituximab alone, non-anthracycline containing regiments and previously observed only are eligible
Non-Hodgkin’s lymphoma (NHL) or Hodgkin’s lymphoma (HL) beyond first remission
All risk by Follicular Lymphoma International Prognostic Index (FLIPI) 0-5 factors
Burkitt lymphoma
lymphoma
Adults with histologically proven solid malignancy, high-grade lymphoma or low-grade lymphoma
Transformed lymphoma
Patients with indolent non-Hodgkin lymphoma (NHL) must have had >= 1 regimen of rituximab-containing regimen; Note: this includes follicular lymphoma (FL), marginal lymphoma and mucosa-associated lymphoid tissue (MALT)
History of indolent lymphoma
History of follicular lymphoma grade 3B
Burkitt lymphoma
Refractory to chemotherapy lymphoma
Patients with indolent lymphoma must have an indication for treatment in the opinion of the investigator
Follicular Lymphoma I, II, IIIA
Lymphoplasmocytic lymphoma
Measurable or assessable lymphoma
Patients with a low grade lymphoma or CLL and a concurrent high grade lymphoma transformed from the low grade lymphoma or CLL will be eligible
Transformation to high-grade lymphoma secondary to previously untreated low-grade lymphoma.
No prior treatment for lymphoma
Follicular lymphoma G1-2-3a
Previously untreated diffuse large B-cell lymphoma or grade 3B follicular lymphoma (of any stage); subjects must be planned to receive full course (6 cycles) of RCHOP chemoimmunotherapy as per clinical standard of care; patients may have de novo DLBCL, and /or any of the following:\r\n* Composite lymphomas, which include both diffuse DLBCL and another histology (most commonly follicular lymphoma) in the same lymph node\r\n* Transformed lymphoma with DLBCL histology, as long as the patient has not received prior therapy for lymphoma\r\n* Discordant presentations, such as DLBCL in a lymph node  and low-grade lymphoma such as follicular lymphoma in the bone marrow
Histologies of myeloma or lymphoma
Only 1 line of previous anti-lymphoma therapy is allowed and not currently receiving any other agent that would be considered as a treatment for the lymphoma; patients must be >= 2 weeks from prior anti-lymphoma therapy; the use of steroids and/or rituximab up to 1 week prior to registration for management of symptoms is allowed
All cancer diagnoses, except lymphoma, will be eligible
Diagnosis of lymphoma
Inclusion Criteria:\n\n        -- Age ?18 years\n\n          -  Histologically confirmed Follicular Lymphoma (Grade 1, 2 or 3a), Marginal Zone\n             Lymphoma, or Mantle Cell Lymphoma\n\n          -  Must have documented relapsed, refractory or Progressive Disease after last treatment\n             with systemic therapy\n\n          -  Bi-dimensionally measurable disease\n\n          -  Eastern Cooperative Oncology Group (ECOG) Performance status ? 2\n\n          -  Adequate bone marrow function\n\n          -  Willingness to follow pregnancy precautions\n\n        Exclusion Criteria:\n\n          -  Histology other than follicular or marginal zone lymphoma or clinical evidence of\n             transformation or Grade 3b follicular lymphoma\n\n          -  Any medical condition (other than the underlying lymphoma) that requires chronic\n             steroid use\n\n          -  Subjects taking corticosteroids during the last 1 week prior treatment, unless\n             administered at a dose equivalent to < 20 mg/day of prednisone\n\n          -  Systemic anti-lymphoma therapy within 28 days or use of antibody agents within 8 weeks\n             use of radioimmunotherapy within 3 months\n\n          -  Known seropositive for or active viral infection with hepatitis B virus (HBV),\n             hepatitis C virus (HCV), human immunodeficiency virus (HIV)\n\n          -  Known sensitivity or allergy to murine products\n\n          -  Presence or history of central nervous system involvement by lymphoma. Subjects who\n             are at a risk for a thromboembolic event and are not willing to take prophylaxis for\n             it.\n\n          -  Any condition that places the subject at unacceptable risk if he/she were to\n             participate in the study or that confounds the ability to interpret data from the\n             study.
Known secondary HPS that is otherwise treatable (e.g. non-Hodgkin’s lymphoma)
Follicular lymphoma(FL) grade1-2-3a
Patients will be ineligible if they have a lymphoma diagnosis
Lymphoma\r\n* Relapsed lymphoma with residual disease that appears to be chemo-sensitive and non-bulky (< 5 cm at largest diameter)
Absolute neutrophil count (ANC) > 1000 unless impairment is due to lymphoma or immune-mediated mechanism caused by lymphoma
Platelets > 100,000 unless impairment is due to lymphoma or immune-mediated mechanism caused by lymphoma
Histologically confirmed diagnosis of B-cell follicular lymphoma (FL), and grade limited to 1, 2, or 3a based on criteria established by the WHO 2008 classification of tumors of hematopoietic and lymphoid tissues
Confirmed diagnosis of low tumour burden, CD20+ follicular lymphoma
Histologically confirmed follicular lymphoma, grade 1-3a.
Prior chemotherapy for lymphoma
Previous history of indolent lymphoma treated with more than 1 multi-agent chemotherapy regimen or previous cancer therapy for recurrent DLBCL or Grade 3b follicular lymphoma
Known central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation from an indolent lymphoma to a high-grade or DLBCL
Treatment-naive patients with histologically confirmed systemic de novo or transformed diffuse large B-cell lymphoma (DLBCL) (from follicular or marginal zone lymphoma), or follicular lymphoma (FL) Grade 3b;
Previous history of treated indolent lymphoma
Fluorodeoxyglucose-avid lymphoma (i.e., PET-positive lymphoma)
Grade 3b follicular lymphoma
Any prior treatment for non-Hodgkin’s lymphoma
A diagnosis of follicular lymphoma (grades 1, 2, or 3a), untreated
Grade 3b follicular lymphoma
Fluorodeoxyglucose-avid lymphoma
Patients with follicular lymphoma must have received at least two prior therapies
Patients with histologically confirmed aggressive hematologic malignancies with chemotherapy-refractory disease; chemotherapy refractory disease is defined as one or more of the following: stable disease or progressive disease as best response to most recent chemotherapy containing regimen or disease progression or recurrence within 12 months of prior autologous or allogeneic stem cell transplant; subjects must have received adequate prior therapy including at a minimum: anti-cluster of differentiation (CD)20 monoclonal antibody unless tumor is CD20-negative, an anthracycline containing chemotherapy regimen; subjects with transformed follicular lymphoma (FL) must have received prior chemotherapy for follicular lymphoma and subsequently have chemo-refractory disease after transformation to diffuse large B-cell lymphoma (DLBCL)
Participants with transformed lymphoma
Histology other than follicular or marginal zone lymphoma or clinical evidence of transformation or Grade 3b follicular lymphoma.
Platelets >= 100 x 10^9/L or >= 50 x 10^9/L (if related to lymphoma)
No prior anti-lymphoma treatment.
Composite lymphoma or transformed lymphoma.
Histologically documented CD20-positive lymphoma and fluorodeoxyglucose (FDG)-avid lymphoma (that is PET-positive lymphoma) with at least one bi-dimensionally measurable lesion
Grade 3b follicular lymphoma
Have had no prior systemic treatment for lymphoma
Follicular lymphoma (FL) grade 1-2-3a.
Histologically confirmed diagnosis of B-cell indolent Non-Hodgkin lymphoma with histological subtype limited to follicular lymphoma or marginal zone lymphoma, at initial diagnosis and without evidence of pathological transformation or clinical signs suggesting transformation
Diagnosis of lymphoma
Prior history of indolent lymphoma
Follicular lymphoma (FL) grade 1-2-3a
Histologically confirmed follicular lymphoma grade 1, 2 or 3a, Stage II-IV
Have no prior systemic treatment for lymphoma
Symptomatic follicular lymphoma requiring treatment.
Clinical evidence of transformed lymphoma or Grade 3b follicular lymphoma.
For participants with follicular lymphoma: requirement for treatment according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
Grade 3b follicular lymphoma, small lymphocytic lymphoma or Waldenström's macroglobulinaemia
For participants with follicular lymphoma: prior treatment for non-Hodgkin's lymphoma with chemotherapy, immunotherapy, or radiotherapy
For participants with non-follicular lymphoma: prior treatment with chemotherapy or immunotherapy
Patient has histologically confirmed diagnosis of follicular lymphoma or Hodgkin lymphoma
More than one prior line of any systemic chemoimmunotherapy for follicular lymphoma
Transformed lymphoma
Prior treatment for follicular lymphoma
Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma
For patients with non-Hodgkin’s lymphoma, they must be determined to have at least stable disease to last therapy
TIER I SUBJECTS: Histologically confirmed follicular lymphoma (grade 1, 2 or 3) by the World Health Organization (WHO) classification; all pathology must be confirmed at either Brigham and Women's Hospital or Massachusetts General Hospital; a repeat biopsy confirming the above histologies must be performed prior to enrollment if there is clinical suspicion that the patient has transformed to a more aggressive lymphoma
TIER II SUBJECTS: Histologically confirmed follicular lymphoma (grade 1, 2 or 3) by the WHO classification; all pathology must be confirmed at either Brigham and Women's Hospital or Massachusetts General Hospital; a repeat biopsy confirming the above histologies must be performed prior to enrollment if there is clinical suspicion that the patient has transformed to a more aggressive lymphoma
Lymphoma accessible for sampling or existing cryopreserved lymphoma tumor judged suitable for preparation of vaccine
Any component of transformed follicular lymphoma
Follicular lymphoma (FL) Grade 1, 2, or 3a
Previous history of treated indolent lymphoma
Transformation Follicular Lymphoma (TFL)
Confirmed diagnosis of low tumor burden, CD20-positive follicular lymphoma
Follicular lymphoma (FL)
Diagnosis of CD20+, follicular lymphoma that has not been treated
CD20-immunophenotyping of tumor to document B-cell follicular lymphoma
Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B follicular lymphoma
Participants must have histologically confirmed follicular lymphoma (FL) of Grade 1, 2, or 3a
Has enlarged lymph node(s) highly suspicious of lymphoma; or has been diagnosed with lymphoma but is untreated; or has persistent recurrent, or progressive lymphoma
Pathologically confirmed diagnosis of mantle cell lymphoma, follicular lymphoma Grade 3, diffuse large B-cell lymphoma (DLBCL), including transformed follicular histology, Burkitt lymphoma, or B-lineage lymphoblastic lymphoma
Follicular Lymphoma (FL) must have at least 1 lesion that can be biopsied at screening and on treatment
Prior therapy for lymphoma
Follicular lymphoma Grades 1, 2, 3 A
Lymphoplasmacytic lymphoma
One or more of the following lymphoma-related symptoms:
presence of lymphoma-related complications, including narrowing of ureters or bile ducts, tumor-related compression of a vital organ, lymphoma-induced pain, cytopenias related to lymphoma/leukemia, splenomegaly, pleural effusions, or ascites
Corticosteroids for treatment of lymphoma within 28 days of study entry Chronically administered low-dose corticosteroids (e.g., prednisone ?20 mg/day) for indications other than lymphoma or lymphoma-related complications are permitted
Inclusion Criteria:\n\n          1. Previously untreated stage IV indolent B-cell lymphoma [Amendment May 2001:\n             eligibility restricted to follicular lymphoma]\n\n          2. Age <76\n\n        Exclusion Criteria:
No prior chemotherapy for lymphoma
Patients with follicular, grade 1 or 2 non-Hodgkin lymphoma with a FLIPI (Follicular Lymphoma International Prognostic Index) score of 0-2, with no anticipated need for treatment within the next 5 months are considered eligible for this study, regardless of previous treatment history
Survivors of mediastinal lymphoma (either non-Hodgkin’s lymphoma or Hodgkin’s lymphoma) with no active malignancy
Histologies of myeloma or lymphoma
Patients with transformed lymphoma (e.g., Richter's transformation arising in follicular lymphoma or chronic lymphocytic leukemia)
Follicular lymphoma Grade 3B
Patients with transformed lymphoma (e.g., Richter's transformation arising in follicular lymphoma or chronic lymphocytic leukemia)
Patients with transformed lymphoma (e.g., Richters transformation arising in follicular lymphoma or chronic lymphocytic leukemia)
History of lymphoma
Follicular variant
Diagnosis of World Health Organization (WHO) diffuse large B-cell lymphoma, high grade B-cell lymphoma not otherwise specified, or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma
Participant must have a histologic diagnosis of a mature B cell lymphoma (e.g., Burkitt lymphoma/leukemia, atypical Burkitt lymphoma, diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, mature B-cell lymphoma not-otherwise specified [NOS]) as defined in the World Health Organization (WHO) classification
PARTICIPANTS FROM COLLABORATING SITES PARTICIPATING IN BIOLOGICAL OBJECTIVES ONLY: Participant must have a histologic diagnosis of a mature B cell lymphoma (e.g., Burkitt lymphoma/leukemia, atypical Burkitt lymphoma, diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, mature B-cell lymphoma NOS) as defined in the WHO classification
Anaplastic large cell lymphoma (ALCL); or
Known histological transformation from indolent NHL to diffuse large B-cell lymphoma.
Relapsed or refractory diffuse large B cell lymphoma with measurable disease as determined by Non-Hodgkin's Lymphoma Cheson response criteria (2014)
History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL)
Patients must have a histological diagnosis of any of the following (all stages allowed):\r\n* Diffuse large b-cell lymphoma (DLBCL) (including transformation from a previously indolent non-Hodgkin lymphoma [NHL], so long as no prior systemic treatment was given for the indolent NHL)\r\n* B-cell lymphoma, unclassifiable\r\n* Burkitt lymphoma\r\n* MYC+ plasmablastic lymphoma by histology
Anaplastic large cell lymphoma (ALCL), ALK positive
Primary cutaneous type anaplastic large cell lymphoma
Primary mediastinal (thymic) large B-cell lymphoma (PMBL)
1. Diffuse Large Cell Lymphoma (NOT primary mediastinal B-cell lymphoma) -2. Burkitt's Lymphoma
Histologically confirmed diagnosis of a histiocyte/dendritic cell neoplasm or relapsed/refractory aggressive lymphoma with at least one of the following features (with review required at a participating study center):\r\n* Diffuse large B cell lymphoma with Epstein-Barr virus (EBV) positive tumor cells (defined as positive EBV-encoded ribonucleic acid [RNA] in tumor cells)\r\n* Plasmablastic lymphoma\r\n* T cell/histiocyte rich diffuse large B-cell lymphoma (DLBCL)\r\n* EBV+ T cell lymphoma of any histology; note, patients with angioimmunoblastic T cell lymphoma will be eligible regardless of EBV status\r\n* Histiocytic sarcoma\r\n* Follicular dendritic cell sarcoma\r\n* Interdigitating dendritic cell sarcoma
History or diagnosis of mantle cell lymphoma or anaplastic large cell lymphoma.
Diffuse large B cell lymphoma (DLBCL). Histology based upon bone marrow biopsies and/or fine needle aspirates as the sole means of diagnosis are not acceptable.
A histologically confirmed diagnosis of mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL) de novo or in the setting of transformation from an indolent lymphoma (including DLBCL not otherwise specified) according to the World Health Organization criteria for diagnosis of NHL; AND
Untreated ALK+ anaplastic large cell lymphoma (ALCL)
Patients with large cell transformation of cutaneous T cell lymphoma are eligible
Histologically confirmed relapsed or refractory extranodal NK/T-cell lymphoma (ENKTL), nasal type, or EBV-associated diffuse large B cell lymphomas
Pathologically proven diffuse large B-cell lymphoma
Patients with large cell transformation of cutaneous T cell lymphoma are eligible
Histologically confirmed NHL: diffuse large B-cell lymphoma and follicular lymphoma (Grade 1-3A) that has progressed following at least 1 line of prior anticancer therapy.
Patients with peripheral T-cell lymphoma (including but not limited to peripheral T-cell lymphoma, not otherwise specified [PTCL-NOS], angioimmunoblastic T-cell lymphoma, anaplastic large T-cell lymphoma). Patients with mycosis fungoides with large cell transformation with measurable disease is eligible.
Patients must have B-cell non-Hodgkin lymphoma, including mantle cell, follicular, lymphoplasmacytic, marginal zone, transformed indolent B cell lymphoma (including transformed chromic lymphoid leukemia [CLL]), or diffuse large B cell lymphoma that has relapsed after a response to at least one prior therapy regimen or is refractory to prior therapy; patients with de novo diffuse large B-cell lymphoma (DLBCL) must meet one of the following criteria:\r\n* Biopsy-proven refractory disease after a frontline regimen containing both an anthracycline and rituximab or other anti-CD20 antibody (i.e. “primary refractory”), where any disease recurring within 6 months of completion of the regimen is considered refractory\r\n* Relapsed or refractory disease after at least one of the following:\r\n** At least 2 lines of therapy (including at least one with an anthracycline and anti-CD20 antibody)\r\n** Autologous stem cell transplant\r\n** Allogeneic stem cell transplant
Patients must have a diagnosis of B-cell lymphoma confirmed by Laboratory of Pathology, National Cancer Institute (NCI), that is relapsed from or refractory to prior therapy as follows:\r\n* Cohort 1: B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (i.e., Gray-zone lymphoma or GZL)\r\n* Cohort 2: Extranodal diffuse large B-cell lymphoma involving one or more of the specified extranodal sites (i.e., extranodal DLBCL); the following subtypes are included (they do not have to be confirmed as non-germinal center B-cell [GCB] subtype for study entry):\r\n** Primary central nervous system (CNS) lymphoma (PCNSL)\r\n** Primary testicular lymphoma (PTL)\r\n** Primary breast lymphoma (PBL)\r\n** Primary cutaneous DLBCL, leg-type\r\n** Intravascular large B-cell lymphoma (IVBCL)\r\n** Diffuse large B-cell, not otherwise specified (NOS), activated B-cell type, involving 1 or more extranodal site\r\n* NOTE: For GZL, diagnosis will be in accordance with the 2016 World Health Organization classification of lymphoid malignancies; patients diagnosed with other extranodal DLBCL subtypes or that are not otherwise specified (NOS) must involved at least 1 extranodal site and must be considered non-GCB by local immunohistochemistry algorithms; cases that are non-GCB by the Hans criteria are considered eligible as well as cases of DLBCL that are both CD10+ and MUM1+
Have a histologically confirmed diagnosis of follicular lymphoma, diffuse large B-cell lymphoma, or classical Hodgkin lymphoma according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution\r\n* FL: grade 1, 2, 3A, or 3B are eligible\r\n* DBLCL: transformed indolent lymphomas (TIL), primary mediastinal large B-cell lymphoma (PMBCL), and aggressive B-cell lymphoma unclassified (BCL-U) are eligible\r\n* HL: all classical HL subtypes are eligible except for nodular lymphocyte predominant Hodgkin lymphoma, which is excluded
Phase 1 Part: Patients with pathologically confirmed advanced stage B-cell NHL (Ann Arbor stage 3 or 4) for whom R-CHOP is considered appropriate therapy; newly diagnosed DLBCL, newly diagnosed low grade B cell NHL, and previously treated low grade B cell NHL patients in first relapse after a prior treatment with non-anthracycline containing chemotherapy are allowed; double hit and transformed diffuse large B cell lymphoma are allowed\r\n* Allowed low grade B cell lymphomas will include follicular lymphoma any grade, marginal zone lymphoma including mucosa-associated lymphoid tissue (MALT) lymphoma, indolent mantle cell lymphoma and Waldenstrom's macroglobulinemia
Phase 2 Part: Patients with pathologically confirmed newly diagnosed diffuse large B cell lymphoma (Ann Arbor stage 3 or 4); newly diagnosed double hit and transformed diffuse large B cell lymphoma are allowed
Patients with de novo diffuse large B-cell lymphoma
Histologically confirmed diagnosis of CD19 positive diffuse large B-cell lymphoma (DLBCL) or transformed large cell lymphoma from low grade lymphoma
Patients must have Hodgkin lymphoma, anaplastic large cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, gray zone lymphoma, enteropathy-associated T-cell lymphoma, or extranodal natural killer (NK)/T-cell lymphoma, nasal type
For the purpose of this study, aggressive B-cell NHL will be deemed any lymphoma belonging to one of the following groups according to the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms\r\n* For the purposes of stratification, diagnoses are grouped into 2 categories:\r\n** Category A\r\n*** Burkitt lymphoma\r\n*** Burkitt-like lymphoma with 11q aberration\r\n*** High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements\r\n*** High-grade B-cell lymphoma, not otherwise specified (NOS)\r\n** Category B\r\n*** Diffuse large B-cell lymphoma (DLBCL), NOS\r\n*** Diffuse large B-cell lymphoma (DLBCL), NOS; germinal center B-cell type\r\n*** Diffuse large B-cell lymphoma (DLBCL), NOS; activated B-cell type\r\n*** Large B-cell lymphoma with IRF4 rearrangement\r\n*** T-cell/histiocyte-rich large B-cell lymphoma\r\n*** Primary DLBCL of the central nervous system (CNS)\r\n*** Primary cutaneous DLBCL, leg type\r\n*** Epstein-Barr virus (EBV)+ DLBCL, NOS\r\n*** EBV+ mucocutaneous ulcer\r\n*** DLBCL associated with chronic inflammation\r\n*** Lymphomatoid granulomatosis\r\n*** Primary mediastinal (thymic) large B-cell lymphoma\r\n*** Intravascular large B-cell lymphoma\r\n*** ALK+ large B-cell lymphoma\r\n*** Plasmablastic lymphoma\r\n*** Primary effusion lymphoma\r\n*** Human herpesvirus (HHV)-8+ DLBCL, NOS\r\n*** B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
Previously untreated participants with cluster of differentiation 20 (CD20)-positive DLBCL, including one of the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms: DLBCL, not otherwise specified (NOS) including germinal center B-cell type, activated B-cell type; T-cell/histiocyte-rich large B-cell lymphoma; Epstein-Barr virus-positive DLBCL, NOS; anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma; human herpesvirus-8 (HHV8)-positive DLBCL, NOS; High-grade B-cell lymphoma with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements (double-hit or triple-hit lymphoma); High-grade B-cell lymphoma, NOS
Primary mediastinal (thymic) large B-cell lymphoma
Participants must have histologically (via at least a core or ideally, incisional or excisional biopsy) documented CD20 positive or negative diffuse large B-cell lymphoma (DLBCL)
Patients with B-cell lymphoma who are candidates to autologous stem-cell transplantation: \r\n* Primary refractory or relapsed diffuse large B-cell lymphoma in response to salvage treatment\r\n* Primary refractory or relapsed follicular lymphoma or other indolent B-cell histology in response to salvage treatment\r\n* Chemosensitive mantle-cell lymphoma in first or later line of treatment
Histologically confirmed B-cell non-Hodgkin’s lymphoma (NHL) of any of the following subtypes recognized by the World Health Organization (WHO) classification: Burkitt lymphoma, B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma, or follicular lymphoma; patients with evidence of histological transformation to diffuse large B-cell lymphoma from indolent NHL are eligible
Cohort A will enroll 10 patients with a diagnosis of diffuse large B-cell lymphoma; B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (double hit lymphoma), Burkitt lymphoma, and transformed lymphoma
Relapsed large-cell lymphoma, mantle-cell lymphoma and Hodgkin lymphoma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant
Phase II patients who have received any prior therapy for PEL or KSHV-associated large cell lymphoma
Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; primary mediastinal B-cell lymphoma (PMBCL); or DLBCL transformed from indolent histology with one of the following:\r\n* Persistent disease after first-line chemo-immunotherapy\r\n* Relapse after first-line chemo-immunotherapy and not eligible for autologous hematopoietic stem cell transplant (HCT)\r\n* Relapse or persistent disease after at least two lines of therapy or after autologous HCT
Histologically confirmed follicular lymphoma grade 1-3A, diffuse large B cell lymphoma, and mantle cell lymphoma by World Health Organization (WHO) 2009 classification
Patients with aggressive B cell lymphoma histology, including diffuse large B cell lymphoma (DLBCL) and grade 3 follicular lymphoma
Patients must have a histologically confirmed diagnosis of lymphoma expressing the CD20 antigen and generally must have failed at least one prior standard systemic therapy; the exception will be mantle cell lymphoma (MCL) patients, who may be enrolled while in first complete remission (CR) as well as other select high-risk lymphomas (e.g., Burkitt’s, double hit diffuse large B-cell lymphoma [DLBCL], transformed indolent B-cell non-Hodgkin lymphoma [B-NHL], etc.) in accordance with current transplant standard of care for these patients
Patients must have newly diagnosed, previously untreated diffuse large B-cell lymphoma, mantle cell lymphoma, grade 3B follicular lymphoma, Burkitt lymphoma, peripheral T cell lymphoma not otherwise specified (NOS), natural killer (NK)/T cell lymphoma, or transformed lymphoma
Diffuse large B-cell lymphoma, follicular large cell lymphoma, mantle cell lymphoma, anaplastic large cell lymphoma\r\n* Primary refractory disease\r\n* Relapse/progression after autologous HSCT\r\n* Non-CR after salvage regimen
Previously untreated primary mediastinal diffuse large B-cell lymphoma, CD20 positive.
Patients must have a histologically confirmed diagnosis of aggressive B-cell lymphoma (diffuse large B-cell lymphoma [DLBCL], Burkitt lymphoma [BL], etc.) expressing the CD20 antigen and have failed at least one prior standard systemic therapy
(Monotherapy - Parts A, B, C, D, G, H, J, and K) -- Histologically confirmed advanced malignancy, either: (a) Metastatic or unresectable solid malignancy; or (b) Classical Hodgkin lymphoma (HL), or diffuse large B-cell lymphoma (DLBCL), or indolent lymphoma (including follicular lymphoma [FL])
Aggressive non-Hodgkin lymphoma as follows, provided there is stable disease or better to last therapy:\r\n* Natural killer (NK) or NK-T cell lymphoma, peripheral T-cell lymphoma (including angioimmunoblastic T-cell lymphoma, hepatosplenic T-cell lymphoma, subcutaneous panniculitic T-cell lymphoma, and other variants), T-cell prolymphocytic leukemia, or blastic/blastoid variant of mantle cell lymphoma; or\r\n* Hodgkin or aggressive non-Hodgkin lymphoma that has failed at least one multiagent regimen, and the patient is either ineligible for autologous BMT or autologous BMT is not recommended; eligible subtypes of aggressive non-Hodgkin lymphoma include: mantle cell lymphoma; follicular grade 3 lymphoma; diffuse large B-cell lymphoma or its subtypes, excluding primary central nervous system (CNS) lymphoma; primary mediastinal large B-cell lymphoma; large B-cell lymphoma, unspecified; anaplastic large cell lymphoma, excluding skin-only disease; Burkitt’s lymphoma or atypical Burkitt’s lymphoma (high-grade B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt’s), in complete remission
Have histologically confirmed Diffuse Large B Cell Lymphoma that is either:
History of lymphoid malignancy other than FL (eg, diffuse large B-cell lymphoma)
Documented history of immunohistochemistry (IHC)-confirmed CD20-positive (with no subsequent history of CD20-negativity) B-cell, NHL, including diffuse large B cell (DLBCL), mantle cell, marginal zone, lymphoplasmacytic, follicular, transformed follicular, or primary mediastinal B cell lymphoma
Men and women with recurrent surface immunoglobulin positive B cell non-Hodgkin's lymphoma (NHL) according to WHO classification (including, but not limited to, CLL/SLL, Waldenström's macroglobulinemia [WM], mantle cell lymphoma [MCL], and diffuse large B cell lymphoma [DLBCL) who have met requirements for roll over from their parent protocol and want to continue study drug.
Patients must have a histopathologically confirmed diagnosis of diffuse large B-cell lymphoma (DBLCL) or primary mediastinal large B-cell lymphoma
Confirmation of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma of the following histology at relapse: diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple hit lymphoma [DHL/THL]), and follicular lymphoma Grade 3B per WHO 2016 classification
COHORT 1: patients undergoing high dose chemotherapy with autologous stem cell rescue and “high-risk” disease as defined below:\r\n* Diffuse large cell lymphoma or peripheral T cell lymphoma (including specified World Health Organization [WHO] subtypes) not in computed tomography (CT)-positron emission tomography (PET) complete remission at time of high dose therapy\r\n* Diffuse large cell lymphoma with “double hit” or “double expressor” features\r\n* Diffuse large cell lymphoma or peripheral T cell lymphoma (including WHO specified subtypes) refractory to standard induction therapy OR relapsing within 1 year of treatment OR in greater that second complete remission (CR)\r\n* Mantle cell lymphoma not in CR1\r\n* Multiple myeloma with ONE (or more) of the following high risk features:\r\n** Less than very good partial remission at time of high dose therapy \r\n** High Revised-International Staging System (R-ISS) (stage III – 2 microglobulin >= 5.5 plus lactate dehydrogenase [LDH] > upper limit of normal [ULN] and/or del17p, t(4;14), t(14;16)) at time of diagnosis\r\n** Cytogenetics or fluorescent in situ hybridization (FISH) del17p
Known current or previous histologic transformation from indolent non-Hodgkin lymphoma to diffuse large B-cell lymphoma or other aggressive lymphoma histology.
Relapsed or refractory primary central nervous system (CNS) diffuse large B cell lymphoma (PCNSDLBCL) with a CNS lesion, with cerebrospinal fluid (CSF) relapse with positive CSF cytology, or with ocular relapse with positive ocular tissue biopsy; NOTE: tissue biopsy is not absolutely necessary for CNS tumor unless clinical and radiologic findings strongly suggest other etiologies as per treating physician; initial diagnosis must be made by tissue biopsy; NOTE: patients with B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma are also eligible for the protocol as long as they meet other criteria; patients with typical Burkitt lymphoma are not eligible
Subjects must have histologically confirmed relapsed or refractory non-Hodgkin lymphoma that is not a candidate for standard curative therapy; non-Hodgkin lymphoma (NHL) subtypes include: diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, plasmablastic lymphomas, peripheral T-cell lymphomas, and follicular lymphoma of any grade; cutaneous T-cell and B-cell lymphomas will also be eligible in the dose-escalation phase only
Patients must have histologically or cytologically confirmed primary central nervous system diffuse large B-cell lymphoma; only patients with relapsed or refractory disease are eligible; patients with PCNSL that is only extracranial will not be eligible
Follicular lymphoma with large cell transformation
Biopsy proven lymphoma for which rituximab, etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (R-EPOCH) is appropriate frontline therapy, e.g., Burkitt lymphoma or diffuse large B-cell lymphoma (DLBCL) NHL, including plasmablastic lymphoma and primary effusion lymphoma but not T-cell lymphoma; tissue histology will be reviewed at the treating institution
Patients must have histologically or cytologically confirmed Hodgkin lymphoma, Burkitt’s lymphoma, double-hit lymphoma, other c-Myc positive B-cell lymphoma, diffuse large-B cell lymphoma including those patients with history of transformed follicular lymphoma, mantle cell lymphoma, or peripheral T-cell lymphoma
Patient with newly diagnosed, histologically confirmed, group B or C Burkitt lymphoma or leukemia (acute lymphoblastic leukemia, L3 subtype); diffuse large B-cell lymphoma; or primary mediastinal B-cell lymphoma; patients with group B/C post transplant lymphoproliferative disorder are eligible for the study regardless of whether disease is newly diagnosed
Patients with relapsed diffuse large B-cell lymphoma (DLBCL) or HL that have achieved a positron emission tomography (PET)-negative CR following first salvage chemotherapy
Participants with histologically or cytologically documented diffuse large B-cell lymphoma (DLBCL) must meet at least 1 of the following risk criteria:\r\n* Age-adjusted International Prognostic Index (IPI) score: 2-3 \r\n* Ki-67 >= 80%\r\n* Histologically, or cytologically documented activated B-cell-like (ABC, also known as post-GCB) subtype \r\n* Double hit variant, defined as having v-myc avian myelocytomatosis viral oncogene homolog (MYC) gene rearrangement in the presence of B-cell chronic lymphocytic leukemia (CLL)/lymphoma (BCL) 2 or BCL6 gene rearrangement \r\n** Other aggressive non-DLBCL non-Burkitt non-Hodgkin B-cell lymphoma variants as defined by the 2008 World Health Organization (WHO) classification, including rare CD20 negative B-cell lymphomas (i.e. plasmablastic lymphoma, and primary effusion lymphoma) are also eligible; grade 3B follicular lymphoma is also eligible as long as one the above risk criteria is met
Diagnosis of non-Hodgkin’s lymphoma, transformed B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell or T-cell lymphoma, and deemed a candidate for autologous transplant
Histologically proven Diffuse Large B-Cell Lymphoma of the Activated B-Cell type
Newly diagnosed, previously untreated Diffuse Large B-Cell Lymphoma
Diagnosis of lymphoma histologies other than Diffuse Large B-Cell Lymphoma
History of malignancies, other than Diffuse Large B-Cell Lymphoma, unless the patient has been disease free for 5 years or more
Patients must have biopsy-proven de-novo diffuse large B-cell lymphoma (DLBCL) \r\n* Patients with primary mediastinal lymphoma or testicular lymphoma are not eligible\r\n* Patients with prior or simultaneous diagnosis of indolent lymphoma are not eligible\r\n* Post-transplant lymphoproliferative disorder with DLBCL morphology is ineligible
Diagnosis of relapsed or refractory primary mediastinal large B-cell lymphoma AND
Relapsed/refractory diffuse large B cell lymphoma (DLBCL), relapsed/refractory peripheral T cell lymphoma (PTCL) (all subtypes excluding anaplastic large cell lymphoma), relapsed/refractory Cutaneous T cell lymphoma (CTCL) mycosis fungoides/sezary syndrome (MF/SS), relapsed/refractory primary mediastinal B lymphoma (PMBL), and relapsed/refractory mediastinal gray zone lymphoma (MGZL)
Phase 1 (Cohort T2): Participants with diffuse large B-cell lymphoma (DLBCL), regardless of PIK3CA mutation status
Has confirmed diagnosis of relapse or refractory Multiple Myeloma (enrollment completed), Primary mediastinal Large B cell Lymphoma, non-Hodgkin lymphoma (NHL), Follicular Lymphoma, Diffuse Large B cell lymphoma (enrollment discontinued), Hodgkin lymphoma or Myelodysplastic syndrome (enrollment completed).
Has histologically confirmed diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL) or histologically and/or cytologically confirmed advanced or metastatic solid tumor and have relapsed or refractory disease following at least two lines of prior standard therapy, including alkylator/anthracycline (unless anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy (R-CHOP; rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone or prednisone, or equivalent) AND must be considered unable to benefit from intensification treatment with autologous hematopoietic stem cell transplantation (ASCT), as defined by meeting at least one of the following criteria:
Patients must have Burkitt lymphoma; effective with Amendment J (version date: 06/24/2014), the following histologies were removed: B-cell lymphoma: unclassifiable with features intermediate between diffuse large B–cell lymphoma and Burkitt lymphoma; c-MYC + DLBCL and c-MYC+ plasmablastic lymphoma\r\n* If questions arise related to diagnosis, please contact the National Cancer Institute (NCI) principle investigator, Dr. Mark Roschewski or the NCI study coordinator, A. Nicole Lucas
Primary mediastinal (thymic) large B-cell lymphoma.
History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL)
Histologically proven diffuse large B-cell non-Hodgkin's lymphoma
Follicular lymphoma with evidence of diffuse large B-cell transformation
Patient has histologically confirmed diagnosis of diffuse large B cell lymphoma or follicular lymphoma harboring mutations in CREB binding protein (CREBBP) or E1A binding protein p300 (EP300) with relapsed or refractory disease
Patients with either diffuse large B cell lymphoma or follicular lymphoma will be allowed to enroll after receiving only 1 prior therapy if they are felt to not be a candidate for further systemic chemotherapy
Patients who have undergone high-dose therapy and autologous PBSCT for treatment of CD20+; NOTE: Based on historical experience of the Indiana University (IU) Bone Marrow and Stem Cell Transplantation Program, it is expected that the vast majority of patients will have been transplanted for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, or mantle cell lymphoma; however, any patient transplanted for CD20+ lymphoma will be considered potentially eligible
Part II: Subjects must have relapsed or refractory aggressive B cell NHL including follicular lymphoma (FL) grade 3, diffuse large B cell lymphoma (DLBCL), transformed NHL, mantle cell lymphoma (MCL), or other aggressive B cell NHL histology as per the World Health Organization (WHO) 2008 criteria
Primary mediastinal (thymic) large B-cell lymphoma.
Histologically confirmed diagnosis with review of the diagnostic pathology specimen at one of the participating institutions; eligible histologies are:\r\n* For Arm A: diffuse large B cell lymphoma; patients with a prior history of indolent B-cell non-Hodgkin lymphoma (NHL) are eligible, as long as they have histologically confirmed diffuse large B cell lymphoma (DLBCL) prior to their pretransplant salvage treatment; patients with mediastinal large B cell lymphoma are also eligible\r\n* For Arm B: classical Hodgkin lymphoma (patients with nodular lymphocyte predominant Hodgkin lymphoma [NLPHL] are NOT eligible)\r\nFor Arm C: peripheral T cell lymphoma – eligible subtypes will include peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS); angioimmunoblastic T cell lymphoma (AITL); ALK-negative anaplastic large cell lymphoma (ALCL); enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL); and extranodal NK/T-cell lymphoma (ENKTL); patients with other PTCL histologies, including ALK-positive PTCL, and cutaneous T-cell lymphoma will not be eligible
CD20+Diffuse Large B-Cell Lymphoma.
Diagnosis of lymphoma other than Diffuse Large B-Cell Lymphoma.
Patient has histologically confirmed diagnosis of R/R mantle cell lymphoma, follicular lymphoma or diffuse large B cell lymphoma\r\n* Diffuse large B cell lymphoma patients has received at least 1 prior regimen and received, declined, or is ineligible for autologous or allogeneic stem cell transplant\r\n* Follicular lymphoma patients have received at least 2 lines of therapy\r\n* Mantle cell lymphoma patients has received at least 1 line of therapy\r\n* Allogeneic stem cell transplant recipients be greater than 6 months post transplant, not on immunosuppression for prevention of graft versus host disease for > 3 months and without active graft versus host disease are eligible\r\n* Autologous stem cell transplant recipients must have adequate bone marrow recovery and transfusion independent\r\n* Transformed histologies are permitted
Confirmed treatment-naive de novo cluster of differentiation (CD)20 positive (+) diffuse large B cell lymphoma (DLBCL), regardless of cell of origin, with stage II-IV disease, or stage I disease if 6 cycles of chemotherapy are planned
Phase 1 and Phase 2: confirmed diagnosis of previously treated relapsed and/or refractory mantle cell lymphoma, diffuse large B-cell lymphoma and/or transformed large cell lymphoma (TLCL)
Pathologically documented relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL)
Known central nervous system (CNS) disease (NHL, diffuse large B cell lymphoma [DLBCL])
Research participants enrolled are patients with an indication to be considered for HSCT, who are diagnosed with intermediate or high grade B-cell non-Hodgkin lymphoma (NHL) (e.g. diffuse large B-cell lymphoma [DLBCL], mantle cell lymphoma [MCL], or transformed NHL), and that have either (1) recurrence/progression following prior therapy, or (2) verification of high-risk disease in first or subsequent remission
Patients must have histologically confirmed B-cell NHL; acceptable subtypes of B-cell NHL include follicular lymphoma (grades 1, 2, or 3a), marginal zone lymphoma, or lymphoplasmacytic lymphoma/Waldenstrom‘s macroglobulinemia; patients with mantle cell lymphoma must have a documented t(11;14) or overexpression of cyclin D1 by immunohistochemical evaluation; patients with diffuse large B cell lymphoma must have activated B cell subtype as defined by the Hans criteria; however, patients with a history of large cell transformation are eligible provided that there is no current clinical evidence of active transformed lymphoma
Exploratory Cohort: Patients with histologically confirmed relapsed or refractory germinal center (GC)-derived B-Cell lymphoma (diffuse large B-cell [DLBCL] and follicular lymphoma [FL]) defined by the WHO and Hans criteria with no accepted curative options
Histologically confirmed B-cell non-Hodgkin’s lymphoma (NHL) of any of the following subtypes recognized by the World Health Organization (WHO) classification: diffuse large B-cell lymphoma, mantle cell lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, or follicular lymphoma; patients with evidence of histological transformation to diffuse large B-cell lymphoma from indolent NHL are eligible
Curative therapy must have been exhausted or not feasible to administer; patients with diffuse large B-cell lymphoma, germinal center subtype should only enroll on the study if there are no other potentially effective therapeutic options
No prior treatment for diffuse B-cell lymphoma (DLBCL)
Participants must have histologically confirmed Hodgkin lymphoma or non-Hodgkin lymphoma, (including, but not limited to, diffuse large B-cell lymphoma [DLBCL] or primary mediastinal B-cell lymphoma [PMBCL], Ann Arbor stage I-II disease, or stage III-IV disease with a dominant presenting mass within the mediastinum); pathology must be reviewed and confirmed at Massachusetts General Hospital (MGH) or other Dana-Farber (DF)/Harvard Cancer Center (HCC) institution
Patients must have previously treated relapsed and/or refractory MCL, follicular lymphoma grade 1-3, marginal zone lymphoma, or non-germinal center B-cell diffuse large B-cell lymphoma with 1-4 prior lines of therapy; (prior anthracycline, rituximab or stem cell transplant [autologous (auto) or allogeneic (allo)] are acceptable)
Histologically confirmed diagnosis of grade 3b follicular lymphoma (FL), transformed indolent lymphoma, diffuse large B-cell lymphoma (DLBCL), mediastinal large B-cell lymphoma, mantle cell lymphoma (MCL), peripheral T-cell lymphoma unspecified, or anaplastic large cell lymphoma primary systemic type, or angioimmunoblastic T cell lymphoma.
Subject (non-diffuse large B-cell lymphoma) must have relapsed or refractory non-Hodgkin's lymphoma, and require treatment in the opinion of the investigator.
Subject has refractory diffuse large B-cell lymphoma, defined as meeting any of the following criteria:
Diagnosis of refractory or relapsed biopsy-proven CD20+ diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma
Histologically or cytologically proven B-cell malignancies, either Burkitt lymphoma or B-AL (=Burkitt leukaemia = L3-AL) or diffuse large B-cell NHL or aggressive mature B-cell NHL non other specified or specifiable.
Central nervous system lymphoma, leptomeningeal lymphoma, or histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
The following disease types are eligible: transformed lymphomas: diffuse large B cell lymphoma, mantle cell lymphoma, follicular lymphoma grade III; precursor B lymphoblastic leukemia/lymphoma; mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma/leukemia; precursor T-lymphoblastic leukemia/lymphoma; primary cutaneous anaplastic large cell lymphoma; anaplastic large cell lymphoma – primary systemic type; small lymphocytic lymphoma/chronic lymphocytic leukemia; follicular lymphoma, grades 1, 2; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphatic tissue (MALT) type; nodal marginal zone B-cell lymphoma; splenic marginal zone B-cell lymphoma; peripheral T cell lymphoma, unspecified; anaplastic large cell lymphoma (T and null cell type); lymphoplasmacytic lymphoma (Waldenstrom Macroglobulinemia); CNS lymphoma; post transplant lymphoproliferative disorders; mycosis fungoides/Sezary syndrome; primary effusion lymphoma; blastic natural killer (NK)-cell lymphoma; adult T-cell leukemia/lymphoma; extranodal NK/T-cell lymphoma, nasal type; enteropathy-type T-cell lymphoma; hepatosplenic T-cell lymphoma; subcutaneous panniculitis-like T-cell lymphoma; angioimmunoblastic T-cell lymphoma; anaplastic large cell lymphoma – primary cutaneous type; T-cell prolymphocytic lymphoma
Histologic documentation of diffuse large B-cell lymphoma, or any of its variants as defined in the World Health Organization (WHO) classification, including but not limited to any of the following:\r\n* Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS)\r\n* Primary mediastinal DLBCL\r\n* T cell/histiocyte-rich large B-cell lymphoma
Central nervous system lymphoma or prior diffuse large B-cell lymphoma (DLBCL), histological evidence of transformation to high grade or diffuse large B-cell lymphoma
Patient must have a CD19-expressing B cell lymphoma; patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and diffuse large B-cell lymphoma transformed from follicular lymphoma must have measurable disease after at least two prior chemotherapy regimens one of which must have contained doxorubicin and rituximab
Diffuse large B-cell lymphoma, follicular large cell lymphoma, peripheral T-cell lymphoma, mantle cell lymphoma, anaplastic large cell lymphoma\r\n* Primary refractory disease\r\n* Relapse/progression after autologous HSCT after autologous HSCT\r\n* Stable disease or better response to last therapy
Histologically or cytologically documented newly diagnosed (stages II, III or IV) Myc-positive diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma, or high-grade unclassifiable with features intermediate between DLBCL and Burkitt lymphoma (per the 2008 World Health Organization [WHO] classification of lymphoid neoplasm) OR histologically or cytologically-documented newly diagnosed (stages II, III or IV) DLBCL not otherwise specified (NOS) or high-grade B-cell lymphoma with Myc and B-cell lymphoma 2 (Bcl2) and/or B-cell lymphoma 6 (Bcl6) (per the 2016 revision of the WHO classification of lymphoid neoplasms)
Treatment-naive patients with systemic de novo or transformed diffuse large B cell lymphoma (DLBCL) or follicular non-Hodgkin lymphoma (NHL) grade 3b
Diffuse Large B Cell Lymphoma (DLBCL)
Primary Mediastinal Large B Cell Lymphoma (PMBCL)
Relapsed/refractory diffuse large B cell lymphoma (DLBCL) is allowed if the patient is not eligible for, or refuses, hematopoietic stem cell transplant
Metastatic renal cell carcinoma, mantle cell lymphoma, or diffuse large B-cell lymphoma including Grade 3b follicular lymphoma
Diagnosis of mantle or diffuse large-cell lymphoma, Grade 3B follicular lymphoma [Harris, Swerdlow et al. 2008] or gastric mucosa-associated lymphoid tissue (MALT) lymphoma
Evidence of transformation to a high grade or diffuse large B-cell lymphoma
Known histological transformation from iNHL to diffuse large B-cell lymphoma.
Diagnosis of Primary Mediastinal Large B-cell Lymphoma
Group 3: Individuals with lymphoma are limited to diffuse large B-cell lymphoma and peripheral T-cell lymphoma that are refractory to or intolerant of standard therapy or for which no standard therapy is available
Patients with mantle cell lymphoma, T-cell lymphoma, and diffuse large B-cell lymphoma within 6 months post autologous transplantation and without relapse
Patients must have histologically proven relapsed or refractory B-cell NHL of the following World Health Organization (WHO) classification subtypes: follicular lymphoma (FL), mantle cell lymphoma (MCL), lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia (LPL/WM), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma (BL), and B-cell lymphoma with features unclassifiable between Burkitt’s and large cell lymphoma; alternatively, patients with histologically proven, newly diagnosed transformed non-Hodgkin’s lymphoma (tNHL) are eligible
Patient has a histologically confirmed diagnosis of mantle cell lymphoma, follicular lymphoma, or diffuse large B cell lymphoma.
Patients must have biopsy confirmed, cluster of differentiation (CD)20 positive diffuse large B-cell lymphoma, mantel cell, high grade-B-cell or anaplastic large B cell non-Hodgkin lymphoma (NHL); AND bone marrow must show =< 20% CD20+ B-cells with >= 15% cellularity within 42 days of study registration
Untreated, histological diagnosis of CD20-positive diffuse large B-cell lymphoma
Histologically confirmed relapsed or refractory CD20+ DLBCL, transformed indolent lymphoma (follicular or other), or primary mediastinal large B-cell lymphoma;
PHASE II: Histological confirmation of transformation of FL lymphoma to diffuse large B cell lymphoma or aggressive lymphoma
Histologically documented PCNSL or histologically documented systemic diffuse large B-cell lymphoma (DLBCL)
Subjects with a diagnosis of lymphoma falling into the following categories:\r\n* Diffuse large B-cell lymphoma (DLBCL) who have received 1 cycle of anthracycline-based chemotherapy\r\n* DLBCL in complete remission and within 12 months after completion of anthracycline-based chemotherapy\r\n* Chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) receiving ibrutinib for at least 1 month\r\n* Follicular lymphoma (FL) in remission and on surveillance for 6 or more months\r\n* Aggressive peripheral T-cell lymphoma (PTCL) who have received 1 cycle of chemotherapy
Patients with aggressive non-Hodgkin’s lymphoma (NHL), including diffuse large cell lymphoma, mediastinal B-cell lymphoma, transformed lymphoma, mantle cell lymphoma, and peripheral T cell lymphoma, who also have one of the following criteria:\r\n* Failure to achieve complete remission to primary induction therapy\r\n* Relapsed and refractory to at least one line of salvage systemic therapy\r\n* Failed stem cell collection
Non-Hodgkin lymphoma (NHL) subjects with anaplastic lymphoma kinase (ALK) negative CD30+ anaplastic large-cell lymphomas (ALCL), CD30+ ALCL regardless of ALK status, with chemotherapy-sensitive relapse, CD30+ high-risk diffuse large B-cell lymphoma (DLBCL), CD30+ cutaneous T cell lymphoma, or CD30+ mycosis fungoides who are otherwise eligible for transplant, are eligible for this study
Study 1 - Aggressive lymphoma\r\n* Newly diagnosed de-novo DLBCL or primary mediastinal B-cell lymphoma that will be treated with an anthracycline-containing regimen (rituximab-cyclophosphamide, doxorubicin hydrochloride, prednisone [R-CHOP] or equivalent) \r\n* Patients with composite lymphomas (low grade and large cell; marginal and large cell; nodular lymphocyte predominant [LP] Hodgkin and large cell, etc) at the time of original diagnosis can also be enrolled as long as they have large cell component and will be treated with an anthracycline\r\n* Patients with high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6 (formerly DLBCL with double or triple hit), high-grade B-cell lymphoma, not otherwise specified (NOS), B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma, and post-transplant DLBCL are also eligible as long as they meet other criteria and are receiving RCHOP-based therapy\r\n** NOTE: patients can be enrolled up through day 1 of cycle 3 of therapy; the patient is permitted to participate in any other therapeutic therapy for their disease as long as it does not concern vitamin D; patients can begin their chemotherapy while awaiting vitamin D results and treatment arm assignment or\r\n* Newly diagnosed untreated peripheral T-cell non-Hodgkin lymphoma (NHL) that will be treated with chemotherapy; NOTE: patients can be enrolled up through day 1 of cycle 3 of therapy; this includes the following disease types:\r\n** Peripheral T cell lymphoma, unspecified\r\n** Anaplastic large cell lymphoma (T and null cell type)\r\n** Extranodal NK/T-cell lymphoma, nasal type\r\n** Enteropathy-type T-cell lymphoma\r\n** Hepatosplenic T-cell lymphoma\r\n** Subcutaneous panniculitis-like T-cell lymphoma\r\n** Angioimmunoblastic T-cell lymphoma\r\n** Anaplastic large cell lymphoma – primary cutaneous type and\r\n* Willing to provide tissue for correlative research purposes
Patients who previously had indolent lymphoma and now at a separate episode have large cell NHL (i.e. transformation)
Diffuse large B-cell lymphoma (DLBCL) Not otherwise specified (NOS) including transformed indolent Non-Hodgkin lymphoma (NHL)
T cell/histiocyte-rich large B-cell lymphoma
Primary mediastinal (thymic) large B-cell lymphoma
Diffuse Large B Cell Lymphoma (DLBCL)
Pathologically confirmed relapsed/ refractory DLBCL
History of transformation of indolent disease to DLBCL (expansion-phase only)
Subjects with DLBCL, BCLu, HGBCL NOS, or HGBCL with translocations of MYC and BCL2 and/or BCL6, must have had no prior chemotherapy for lymphoma. Steroids for palliation prior to enrollment are allowed.
Pathologically confirmed de novo DLBCL
Have previously received at least 2 but no more than 5 previous systemic regimens for the treatment of DLBCL
DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (HL+NHL) or DLBCL transformed from diseases other than indolent NHL.
Participantts with diffuse large B-cell lymphoma (DLBCL) relapsed or refractory to ? 1 course of chemotherapy including an anti-CD20 monoclonal antibody, and not eligible for autologous stem cell transplantation (ASCT) (including due to chemorefractory disease). Participants with transformed FL are eligible, provided DLBCL histology is biopsy-confirmed prior to study entry and a treatment regimen as described above has been administered. The Sponsor retains the option to limit the number of participants enrolled with transformed FL.
DLBCL, regardless of cell of origin or underlying molecular genetics
INCLUSION CRITERIA:\n\n          1. Age ?18 years\n\n          2. Histologically confirmed diagnosis, according to the World Health Organization (WHO,\n             2008) classification, of: DLBCL NOS, THRLBCL, EBV-positive DLBCL, composite lymphoma\n             with a DLBCL component with a DLBCL relapse subsequent to DLBCL treatment, disease\n             transformed from an earlier diagnosis of low grade lymphoma (i.e. an indolent\n             pathology such as follicular lymphoma, marginal zone lymphoma) into DLBCL with a DLBCL\n             relapse subsequent to DLBCL treatment.\n\n          3. Fresh tumour tissue for central pathology review must be provided as an adjunct to\n             participation in this study. Should it not be possible to obtain a fresh tumour tissue\n             sample, archival paraffin embedded tumour tissue acquired ?3 years prior to screening\n             for this protocol must be available for this purpose.\n\n          4. Patients must have:\n\n               1. relapsed or refractory DLBCL\n\n               2. at least one bidimensionally measurable disease site. The lesion must have a\n                  greatest transverse diameter of ?1.5 cm and greatest perpendicular diameter of\n                  ?1.0 cm at baseline. The lesion must be positive on PET scan\n\n               3. received at least one, but no more than three previous systemic therapy lines for\n                  the treatment of DLBCL. At least one previous therapy line must have included a\n                  CD20-targeted.\n\n               4. ECOG 0 to 2\n\n          5. Patients after failure of ASCT or patients considered in the opinion of the\n             investigator currently not eligible for HDC with subsequent ASCT.\n\n          6. Patients must meet the following laboratory criteria at Screening:\n\n               1. ANC ?1.5 × 109/L (unless secondary to bone marrow involvement by DLBCL)\n\n               2. PLTs ?90 × 109/L (unless secondary to bone marrow involvement by DLBCL) and\n                  absence of active bleeding\n\n               3. total serum bilirubin ?2.5 × ULN unless secondary to Gilbert's syndrome (or\n                  pattern consistent with Gilbert's) or documented liver involvement by lymphoma.\n                  Patients with Gilbert's syndrome or documented liver involvement by lymphoma may\n                  be included if their total bilirubin is ?5 x ULN\n\n               4. ALT, AST and AP ?3 × ULN or <5 × ULN in cases of documented liver involvement by\n                  lymphoma\n\n               5. serum creatinine ?2.0 x ULN or creatinine clearance must be ?40 mL/min calculated\n                  using a standard Cockcroft-Gault formula (Cockroft & Gault, 1976)\n\n          7. For a female of childbearing potential (FCBP), a negative pregnancy test must be\n             confirmed before enrolment. An FCBP must commit to take highly effective contraceptive\n             precautions without interruption during the study and for 3, 6 or 12 months after the\n             last dose of MOR00208, BEN or RTX respectively, whichever is later. An FCBP must\n             refrain from breastfeeding and donating blood or oocytes during the course of the\n             study and for 3, 6 or 12 months after the last dose of MOR00208, BEN or RTX\n             respectively, whichever is later. Restrictions concerning blood donations apply as\n             well to females who are not of childbearing potential.\n\n          8. Males must use an effective barrier method of contraception without interruption\n             during the study and for 3, 6 or 12 months after the last dose of MOR00208, BEN or RTX\n             respectively, whichever is later, if the patient is sexually active with an FCBP.\n             Males must refrain from donating blood or sperm during study participation and for 3,\n             6 or 12 months after the last dose of MOR00208, BEN or RTX respectively, whichever is\n             later.\n\n          9. In the opinion of the investigator, the patients must:\n\n               1. be able to comply with all study-related procedures, medication use, and\n                  evaluations\n\n               2. be able to understand and give informed consent\n\n               3. not be considered to be potentially unreliable and/or not cooperative.\n\n        EXCLUSION CRITERIA:\n\n          1. Patients who have: any other histological type of lymphoma including, e.g., primary\n             mediastinal (thymic) large B-cell lymphoma (PMBL) or Burkitt's lymphoma, primary\n             refractory DLBCL, patients with known \double/triple hit\ DLBCL genetics, CNS lymphoma\n             involvement in present or past medical history\n\n          2. Patients who had a major surgery less than 30 days prior to Day 1 dosing\n\n          3. Patients who have, within 14 days prior to Day 1 dosing:\n\n               1. not discontinued CD20-targeted therapy, chemotherapy, radiotherapy,\n                  investigational anticancer therapy or other lymphoma-specific therapy\n\n               2. received live vaccines\n\n               3. required parenteral antimicrobial therapy for active, intercurrent systemic\n                  infections\n\n          4. Patients who:\n\n               1. in the opinion of the investigator, have not recovered sufficiently from the\n                  adverse toxic effects of prior therapies, major surgeries or significant\n                  traumatic injuries\n\n               2. were previously treated with CD19-targeted therapy or BEN\n\n               3. have a history of previous severe allergic reactions to compounds of similar\n                  biological or chemical composition to MOR00208, RTX, murine proteins or BEN, or\n                  the excipients contained in the study drug formulations\n\n               4. have undergone ASCT within a period of ?3 months prior to signing the informed\n                  consent form. Patients who have a more distant history of ASCT must exhibit full\n                  haematological recovery before enrolment into the study.\n\n               5. have undergone previous allogeneic stem cell transplantation\n\n               6. concurrently use other anticancer or experimental treatments\n\n          5. Prior history of malignancies other than DLBCL, unless the patient has been free of\n             the disease for ?3 years prior to Screening. Exceptions to the ?3-year time limit\n             include history of the following:\n\n               1. basal cell carcinoma of the skin\n\n               2. squamous cell carcinoma of the skin\n\n               3. carcinoma in situ of the cervix, breast and bladder\n\n             f) incidental histological finding of prostate cancer (Tumour/Node/Metastasis [TNM]\n             stage of T1a or T1b)\n\n          6. Patients with:\n\n               1. positive hepatitis B and/or C serology\n\n               2. known seropositivity for or history of active viral infection with HIV\n\n               3. evidence of active, severe uncontrolled systemic infections or sepsis\n\n               4. a history or evidence of severely immunocompromised state\n\n               5. a history or evidence of severe hepatic impairment (total serum bilirubin > 3\n                  mg/dL), jaundice unless secondary to Gilbert's syndrome or documented liver\n                  involvement by lymphoma\n\n               6. a history or evidence of clinically significant cardiovascular, cerebrovascular,\n                  CNS and/or other disease that, in the investigator's opinion, would preclude\n                  participation in the study or compromise the patient's ability to give informed\n                  consent
Primary refractory HL or DLBCL
At least 2 but no more than 4 prior lines of therapy for the treatment of de novo DLBCL and ineligible for (or failed) autologous or allogeneic stem cell transplant (SCT) (salvage therapy, conditioning therapy and maintenance with transplant will be considered one prior treatment). NOTE: For follicular lymphoma transformed to DLBCL (t-FL/DLBCL), single agent non-cytotoxic therapy will not be considered as a line of therapy.
High grade B-cell lymphoma (HGBL), with MYC and BCL2 and/or BCL6 rearrangements or DLBCL, NOS per the 2016 revision of the WHO classification of lymphoid neoplasms (Swerdlow et al, 2016).
Diagnosis of t-FL/DLBCL is allowed. However, other B-cell lymphomas including other transformed indolent lymphomas/DLBCL per the 2008 WHO classification, and Burkitt lymphoma are not eligible.
Known primary mediastinal, ocular, epidural, testicular or breast DLBCL.
Patients with histological confirmation of relapsed/refractory non-GCB type (using Hans algorithm) diffuse large B cell lymphoma (DLBCL) or relapsed/refractory primary CNS lymphoma (PCNSL) with at least one of the following characteristics:\r\n* Definition of refractory disease: progression of disease based on Cheson criteria for DLBCL or international primary CNS lymphoma cooperative group for PCNSL either with nonresponse or progression within 3 months of prior therapy\r\n* Definition of relapsed disease: progression of disease based on Cheson criteria for DLBCL or International primary CNS lymphoma cooperative group for PCNSL at least 3 months after prior therapy\r\n* Definition of non-GCB subtype (Hans algorithm): cases will be subclassified based on immunohistochemical staining with CD10, BCL-6 and MUM-1 as previously described.\r\n* Patients should have exhausted (or be ineligible for) approved therapies known to provide clinical benefit for DLBCL or PCNSL (e.g. high dose chemotherapy with autologous stem cell transplant, chimeric antigen receptor-transduced [CAR-T] therapy, etc.).
Any active malignancy other than DLBCL
Cohort #1: histologically confirmed CD20-positive, relapsed or refractory DLBCL, including de novo and transformed DLBCL (from follicular or marginal zone lymphoma); this includes patients with DLBCL who are found to have small cell infiltration of the bone marrow or other diagnostic material (representing a discordant lymphoma)
Histologically confirmed diagnosis of rel/ref DLBCL, or diffuse large B cell lymphoma transformed from an indolent lymphoma\r\n* Since the endpoint of the phase I portion is safety, any B-cell NHL can be enrolled; however, the progression-free survival (PFS) endpoint varies greatly amongst different types of lymphoma; in order to accurately interpret the survival data, a homogeneous cohort of patients with DLBCL will be evaluated; DLBCL is the most aggressive B-NHL with limited options; other B-NHL’s are generally more indolent and have more options available to them
Have pathologically confirmed DLBCL on biopsy
Patients with DLBCL who best fit the criteria of EBV+ DLBCL, NOS are not eligible
For DLBCL\r\n* Histologically confirmed aggressive B cell non-Hodgkin lymphoma (NHL) including the following types defined by World Health Organization (WHO) 2008: \r\n** DLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr virus (EBV)+ DLBCL of the elderly; OR \r\n** Primary mediastinal (thymic) large B cell lymphoma \r\n** Transformation of follicular lymphoma, marginal zone lymphoma or chronic lymphocytic leukemia to DLBCL will also be included\r\n* Subjects with DLBCL must have progressed, had stable disease (SD), or recurred after initial treatment regimens that include an anthracycline and an anti CD20 monoclonal antibody; subjects who relapse >= 12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant
histologically-confirmed relapsed or refractory CD20+ B-cell lymphoma of one of the following types, with documented disease progression or recurrence following the immediate prior therapy: DLBCL (regardless of cell of origin or underlying molecular genetics), MCL, PMBCL, Gr3b-FL, TH-FL (prior dx of FL before transforming to DLBCL).
Histologically proven DLBCL, including transformation from follicular lymphoma
Received more than one line of therapy for DLBCL
Prior therapy for DLBCL, with the exception of nodal biopsy
Participants with central nervous system (CNS) lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL
DLBCL cohort: DLBCL, not otherwise specified (NOS; includes transformed DLBCL from indolent histology [tDLBCL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (Swerdlow 2016), primary mediastinal B-cell lymphoma (PMBCL), and follicular lymphoma Grade 3B. Subjects must have been treated with an anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease after at least 2 lines of therapy or after auto-HSCT.
Diagnosed with relapsed or refractory de novo DLBCL or follicular lymphoma transformed to DLBCL to one previous line of anthracycline-containing chemotherapy
PHASE II: Histologically confirmed B-cell NHL:\r\n* Cohort 1: with only de novo DLBCL,\r\n* Cohort 2: with only FL of grade 1, 2 or 3a
PART IB: Histologically confirmed B-cell NHL:\r\n* Group 1: with only de novo DLBCL,\r\n* Group 2: with only FL of grade 1, 2 or 3a\r\n* Group 3: with only MCL with t(11;14) or overexpression of cyclin D1\r\n* Group 4: all other NHL including MZL, LL, WM, BL, primary mediastinal B cell lymphoma (PMBCL), gray zone lymphoma (GZL) and patients with histological transformation to DLBCL from indolent lymphoma are eligible
Part 1 (Dose Escalation): Diagnosis of B-cell DLBCL, FL, MCL, or HL, as documented by medical records.
Histologically confirmed diffuse large B-cell lymphoma (DLBCL) or transformed DLBCL
PHASE II: Patients must have histologically confirmed R/R NHL (as defined by World Health Organization [WHO] criteria); in addition, patients with NHL other than diffuse large B cell lymphomas (DLBCL) must have received at least 2 prior therapies; patients with DLBCL will be eligible if there is no available standard therapy
Histologically confirmed CD20-positive DLBCL, any stage, bulky or nonbulky disease
Histologically confirmed DLBCL (WHO classification).
Histopathologically confirmed diagnosis of previously untreated DLBCL of the non-GCB DLBCL subtype
Patients with ABC (determined by immunohistochemistry using the Hans algorithm) diffuse large B-cell lymphoma (DLBCL) with primary refractory disease, relapse < 12 months after initial therapy, secondary International Prognostic Index (IPI) > 1, less than partial response to salvage treatment or exposure to > 3 salvage regimens
For Part 2 and Part 3 of the study, participants must have histopathologically and clinically confirmed diagnosis of relapsed DLBCL. Participants will be considered to have a relapsed disease if they showed a duration of response of at least 24 weeks after their first line of therapy. The following participants with relapsed DLBCL will be enrolled:
For Part 2 and Part 3 of the study, patients with primary refractory DLBCL (defined as progression of disease within 24 weeks after first line of treatment).
Patients with non-Hodgkin lymphoma (NHL) other than DLBCL; including \transformed\ DLBCL
104 For Part 2 (Expansion in patients with DLBCL): only biopsy proven DLBCL (biopsy proven at least at primary diagnosis), including DLBCL that represents transformation of indolent NHL (including follicular, marginal zone, and lymphoplasmacytic lymphoma excluding chronic lymphocytic leukemia or Hodgkin Lymphoma) are eligible. Presentations of these histologies with substantial occurrence of malignant cells into the bloodstream (lymphocyte count ? 7 x 10^9/L) including all leukemic presentations are excluded. Subjects with transformation of indolent lymphoma must have received therapy after a diagnosis of transformation that is appropriate for aggressive histology as described in 105. Other histologies are not eligible.
205 For Part 2 (Expansion in patients with DLBCL): fluorodeoxyglucose non-avid patients.
DLBCL Phase 2 cohort: De novo or transformed diffuse large B-cell lymphoma (DLBCL), relapsed or refractory to frontline or second line treatment or autologous hematopoietic cell transplantation
Pathologically confirmed diagnosis of relapsed or refractory diffuse large B-cell lymphoma (DLBCL; including de novo and transformed DLBCL) or Grade 3b follicular lymphoma
If a subject has de novo DLBCL, the diagnosis is confirmed by biopsy and is immunohistologically characterized as de novo germinal center B-cell-like (GCB) DLBCL or de novo non-GCB DLBCL.
If the subjects has transformed DLBCL, the diagnosis is confirmed by biopsy and is immunohistologically characterized as transformation to DLBCL from indolent lymphoma (eg, follicular lymphoma).
Histologically confirmed DLBCL expressing CD20 antigen; patients with transformed lymphoma are excluded; in this regard, patients with composite lymphoma in the diagnostic tissue (concomitant DLBCL and follicular or other low-grade lymphoma component) are excluded; however, patients with DLBCL in primary diagnostic tissue but a bone marrow that shows low grade or indeterminate lymphoma are eligible; patients with known primary mediastinal large B-cell lymphoma (PMLBCL) are excluded; similarly, patients with known c-myc translocation (by fluorescence in situ hybridization) positive DLBCL are encouraged to participate in trials specifically designed for these patients; however patients with known c-myc DLBC positive are NOT excluded from this study; c-myc testing prior to study enrollment is NOT required
History of histologically documented r/r Grades 1 to 3a FL, or r/r DLBCL
primary refractory DLBCL
Neuropathy uropathy europathy Nemediastinal DLBCL.
Primary mediastinal DLBCL.
Relapsed or refractory de novo or transformed DLBCL disease following at least one prior systemic therapy (for DLBCL)
DLBCL-2 cohort:
For participants with DLBCL: preplanned consolidative radiotherapy
Histologically documented diagnosis of DLBCL.
Phase 1: any DLBCL subtype.
Transformed DLBCL or DLBCL with coexistent histologies (eg, follicular or mucosa-associated lymphoid tissue lymphoma).
History of transformation of indolent disease to DLBCL
Histologically confirmed de novo DLBCL by the 4th edition of the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues published in 2008; patients with a history of indolent lymphoma excluded; patients with known primary mediastinal large B-cell lymphoma (PMLBCL) are excluded; patients with known c-v-myc avian myelocytomatosis viral oncogene homolog (c-myc) translocation (by fluorescence in situ hybridization) positive DLBCL are eligible for enrollment; c-myc testing prior to study enrollment is not required; availability of diagnostic biopsy samples in encouraged for the exploratory analysis but not required for enrollment; patients with \double-hit\ or \triple-hit\ lymphoma are eligible for enrollment
Prior history of low grade lymphoma with transformation to DLBCL; if a patient has a composite diagnosis of DLBCL and low grade without a prior history of lymphoma, they will not be considered ineligible
Pathologically confirmed de novo ABC DLBCL
Confirmation of relapsed or refractory DLBCL or transformed lymphoma (TL)
Histologically-confirmed non-germinal center B-cell subtype DLBCL
DLBCL
Diagnosis of DLBCL (de novo DLBCL, or transformed from indolent lymphoma) or follicular grade 3 lymphoma on the basis of tissue biopsy.
Patients with de novo DLBCL must have received 1-3 treatment regimens for DLBCL. Patients with follicular grade 3 lymphoma must have received 1-3 treatment regimens for follicular lymphoma (any grade). Patients with DLBCL transformed from indolent lymphoma must have received at least 1-4 treatment regimens for NHL.
Patients with DLBCL transformed from indolent lymphoma must have had a complete or partial response to a therapy for NHL lasting at least 12 weeks.
Primary refractory de novo DLBCL or primary refractory follicular grade 3 lymphoma, defined as documented progression within 12 weeks of the last cycle of the first-line multi-agent regimen.
Diagnosis Arm A: CLL (including SLL), DLBCL, or FL; SLL, DLBCL, and FL must be histologically confirmed Arm B: Histologically confirmed SLL or previous confirmation of B-cell CLL with a characteristic immunophenotype by flow cytometry Arm C: Histologically confirmed aggressive B-cell DLBCL, including FL transforming to DLBCL, transformed indolent lymphoma, MCL, or Grade 3b FL, according to the World Health Organization (WHO)/American Joint Committee on Cancer (AJCC) criteria Arm D: Histologically confirmed anti-CD20-refractory (defined as any subject with less than a PR to any prior anti-CD20-based therapy or progression within 6 months after completing therapy with any anti-CD20-based regimen, including maintenance rituximab) aggressive B-cell DLBCL, including FL transforming to DLBCL, transformed indolent lymphoma, MCL, or Grade 3b FL, according to the WHO/AJCC criteria
Histologically confirmed B-cell NHL (FL or DLBCL), transformed indolent lymphoma, and MCL: Measurable disease defined as ? 1 lesion ? 20 mm in one dimension or ?15 mm in 2 dimensions as measured by conventional or high-resolution (spiral) computed tomography (CT). For Arms C and D: disease evaluable by the International Working Group criteria (Cheson et al, 2007)
Baseline PET or PET/CT scans must show positive lesions compatible with CT-defined anatomical tumor sites (only applicable for FL, DLBCL, MCL, transformed indolent lymphoma, and FL transforming to DLBCL) CLL (Arms A and B):
Histologically confirmed B-cell NHL (FL or DLBCL): Relapsed from or refractory to ? 1 prior regimen containing rituximab, either alone or in combination, and not be a candidate for hematopoietic SCT or BM transplant
Has diagnosis and prior treatment for each non-hodgkin's lymphoma (NHL) subtype as defined below: Mantle cell lymphoma (MCL): pathologically verified diagnosis of MCL based on local pathology report, relapsed or refractory disease after at least 2 prior lines of therapy, including at least 1 cycle of Bruton's tyrosine kinase (BTK) inhibitor therapy and documented progressive disease (PD) during or after BTK inhibitor treatment or participants who could not tolerate BTK inhibitor [ie, discontinued BTK inhibitor due to adverse events (AEs)], b) Diffuse large B cell lymphoma (DLBCL): pathologically confirmed diagnosis of non-transformed DLBCL, and relapsed or refractory disease; for those participants who have not received HDT/ASCT are not eligible for HDT/ASCT due to comorbidities, c) Follicular lymphoma (FL): pathologically confirmed diagnosis of FL of Grade 1, 2, or 3a according to World Health Organization (WHO) criteria without pathological evidence of transformation, and relapsed disease after at least two prior systemic therapies including one anti-CD20 containing combination regimen
Histologically confirmed DLBCL, cluster of differentiation (CD)20 positive by flow or immunohistochemistry (IHC); transformed DLBCL is allowed as long as no prior therapy has been given
Prior therapy for DLBCL
No more than 2 prior regimens for DLBCL.
High-grade transformation from earlier diagnosis of low-grade lymphoma; patients with “de novo” transformed diffuse large B-cell lymphoma (DLBCL), defined as DLBCL only on lymph node biopsy and a discordant marrow with para-trabecular small cells at first diagnosis of lymphoma, are eligible if adherent to all other selection criteria
Must have histologically confirmed DLBCL that is relapsed or refractory to previous therapy.
Histologically confirmed DLBCL(Cohort C)
Germinal Center B cell Diffuse large B cell lymphoma (GCB-DLBCL) relapsed or refractory to at least one prior regimen (e.g., rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]) AND not a candidate for standard salvage regimens or autologous or allogeneic stem cell transplant. Local confirmation of lymphoma subtype (e.g. GCB-DLBCL) is allowed for enrollment but must be confirmed through central laboratory testing.
Patients in Parts 2 and 3 must have histologically confirmed diagnosis of CD30-positive DLBCL
History of transformation of indolent disease to DLBCL
for subjects with transformed FL must have received prior chemotherapy for follicular lymphoma and subsequently have chemorefractory disease after transformation to DLBCL
DLBCL of GCB subtype
Diffuse DLBCL with activating mutations in CD79 (A or B subunits) or ABC-subtype DLBCL (CD79 wildtype or CD79 mutant). DLBCL that arose from transformed indolent lymphoma is allowed.
History of transformation of indolent disease to DLBCL
Patients with primary mediastinal DLBCL
Histologically confirmed aggressive B-cell DLBCL, including FL transforming to DLBCL & Grade III FL
Aggressive B-cell lymphoma, including DLBCL and follicular lymphoma (FL) or other indolent or low grade malignancy transforming to DLBCL, grade III FL, Burkitt lymphoma, and unclassifiable B-cell lymphoma with features of Burkitt and DLBCL according to the World Health Organization, with biopsy confirmation of disease which has relapsed after or refractory to a standard cytotoxic chemotherapy combination including rituximab and doxorubicin, for whom an autologous stem cell transplant is planned
Must have histologically confirmed DLBCL, including de novo disease or transformed disease from indolent NHL. a. High-grade B-cell lymphoma (BCL) with MYC and BCL-2 and/or BCL-6 translocations (double-hit DLBCL under DLBCL, not otherwise specified [NOS], based on the 2008 World Health Organization [WHO] classification criteria) is not eligible for this study.
Part 2/Other BCMA positive Hematologic Malignancies cohort: Subject with one of the following lymphomas: Diffuse Large B-cell Lymphoma (DLBCL) or follicular lymphoma (FL) that exhibits positive BCMA expression on tumor cells as determined by a central laboratory using a validated Immunohistochemistry (IHC) assay. Eligible subjects with BCMA positive malignancies must also fulfill the prior treatment requirements as follows: DLBCL: at least 2 prior lines of systemic therapy containing at least one line of chemo-immunotherapy with anti-CD20 antibody, and either has undergone stem cell transplant or is considered transplant ineligible. FL: at least 2 prior lines of systemic therapy.
Chemo-refractory DLBCL (including transformed low grade lymphoma)
Epstein-Barr virus (EBV) positive DLBCL, NOS
Histologically confirmed aggressive B-cell DLBCL, including follicular lymphoma (FL) transforming to DLBCL
Subjects enrolled on the University of Pennsylvania/Abramson Cancer Center (UPCC) 13413 CART-19 autologous T-cell trial with relapsed or refractory DLBCL and FL
For the expansion phase, participants must have histologically confirmed diagnosis of advanced DLBCL or follicular lymphoma FL.