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.