Ages =< 50 years of age with chronic lymphocytic leukemia (CLL)
CLL: must have either 1) failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (FLU) (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); 2) failed FLU-cyclophosphamide (CY)-Rituximab (FCR) combination chemotherapy at any time point; or 3) have “17p deletion” cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in first (1st) CR; 4) patients with a diagnosis of CLL (or small lymphocytic lymphoma) that progresses to prolymphocytic leukemia (PLL); or 5) patients with T-cell CLL or PLL
Histologically confirmed, biopsy-proven diagnosis of DLBCL, BCLu, HGBCL, or TiNHL. Richter's transformation from Chronic Lymphocytic Leukemia (CLL) is not eligible.
Richter's transformation from CLL
Clinical and phenotypic verification of B cell CLL/ SLL/ or monoclonal B-cell lymphocytosis (MBL) and measurable disease; immunophenotyping of the leukemic cells (blood, lymph node, or bone marrow) must demonstrate a monoclonal (kappa or lambda light chain restricted) B cell population with immunophenotype diagnostic for CLL (e.g.: co-expressing CD19 and CD5)
Previously treated for CLL/SLL, but there is not a requirement nor restriction for the specific prior treatments received
Patients who have had prior (within 8 weeks of initiation of DMF) or concurrent antibody therapy directed against CLL (i.e., Rituxan and Campath)
If patient has CLL must have a negative Coombs test
Richter transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma
Relapsed or refractory SLL/CLL, WM, B-cell NHL who have received at least 2 prior lines of systemic therapy.
For CLL subjects, symptomatic disease that mandates treatment (Halleck et al. 2008).
Lymphoma fulfilling the following criteria: Chemotherapy-sensitive (at least stable disease lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are INELIGIBLE for an autologous transplant. Patients with chronic lymphocytic leukemia (CLL) are not eligible regardless of disease status.
Part D only: Patients diagnosed with CLL who are intolerant to, or have disease that is relapsed/refractory after, at least two prior therapies
History of Richter's transformation from CLL
Major inclusion criteria\n\n        Diagnosis/Trial Population\n\n          -  Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL):\n\n               -  history of diagnosis of CLL or SLL that meets IWCLL diagnostic criteria\n\n               -  histologically confirmed diagnosis of SLL by lymph node biopsy\n\n               -  indication for treatment as defined by the IWCLL guidelines\n\n          -  Patients must have both of the following:\n\n               -  relapsed or refractory disease while receiving a BTKi therapy or intolerance of\n                  such therapy\n\n               -  single-agent or combination therapy with a BTKi for at least one month must be\n                  the patient's most recent prior anticancer therapy\n\n          -  ECOG performance status of 0 to 2\n\n          -  Patients with a past medical history of autologous or allogeneic stem cell\n             transplantation must exhibit full hematological recovery\n\n        Laboratory Values\n\n        • Patients must meet adequate bone marrow function and adequate hepatic and renal function\n\n        Other Inclusion Criteria\n\n        • Females of childbearing potential must use a highly effective method of contraception\n\n        Major exclusion criteria\n\n        Diagnosis\n\n        • Patients who have:\n\n          -  non-Hodgkin's lymphomas other than CLL/SLL\n\n          -  transformed CLL/SLL or Richter's syndrome\n\n          -  active and uncontrolled autoimmune cytopenia\n\n        Previous and Current Treatment\n\n          -  Patients who have received treatment with a BTK inhibitor within 5 days prior to Day 1\n             dosing\n\n          -  Patients who have, within 14 days prior to D1 dosing:\n\n               -  not discontinued CD20-targeted therapy, chemotherapy, radiotherapy,\n                  investigational anticancer therapy or other lymphoma specific therapy\n\n               -  systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day\n                  with the exception of patients with signs of rapidly progressing disease\n\n               -  received live vaccines with the exception of vaccination against influenza with\n                  inactivated virus or for pneumococcal diseases
Prior treatment for FL, MZL, SLL, MCL, WM with ? 2 or for CLL or non-GCB DLBCL ? 1 chemotherapy-based or immunotherapy-based regimen, and not transplant eligible and have had either progressive disease (PD) or no response to previous treatment
Presence of lymphadenopathy and/or splenomegaly with histopathological evaluation of a lymph node biopsy consistent with CLL. Clonality of the circulating B-lymphocytes should be confirmed at screening. Previously confirmed immunohistological diagnosis with a characteristic CD5+/CD20+ B--cell immunophenotype according to WHO criteria. CLL diagnosis requires an absolute peripheral blood monoclonal CD20+/CD5+ B-lymphocyte count ? 5000 cells/?L for the duration of at least 3 months. Part 2:
CLL/SLL PATIENTS (ARM A) ONLY
Diagnosis of CLL according to the National Cancer Institute (NCI) criteria or SLL according to the World Health Organization (WHO) criteria; this includes previous documentation of:\r\n* Biopsy-proven small lymphocytic lymphoma or\r\n* Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following:\r\n** Peripheral blood B cell count of > 5 x 10^9/L consisting of small to moderate size lymphocytes\r\n** Immunophenotyping consistent with CLL defined as:\r\n*** The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20 [typically dim expression] or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)\r\n*** Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. immunoglobulin heavy chain variable [IGHV] analysis)\r\n*** NOTE: splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL\r\n** Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescent in situ hybridization (FISH) analysis for t(11;14)(immunoglobulin H [IgH]/cyclin D1 [CCND1]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy
Patients must be previously treated with at least one prior line of therapy; EXCEPTION: CLL patients with Richter’s transformation or Hodgkin transformation do not need prior therapy to enroll\r\n* NOTE:\r\n** Prior chemotherapy or biologic novel therapy or anti-cancer monoclonal antibody based therapy for treatment of CLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments) will not be considered “prior treatment”\r\n** Prior oral corticosteroid therapy for an indication other than CLL will not be considered “prior treatment”\r\n** Previous use of corticosteroids in the combination with other therapy for treatment of autoimmune complications of CLL does constitute prior therapy for CLL
CLL/SLL patients must have progressive disease with any one of the following characteristics based on standard criteria for treatment as defined by the NCI-Working Group (WG) 1996\r\n* Symptomatic CLL characterized by any one of the following:\r\n** Weight loss >= 10% within the previous 6 months\r\n** Extreme fatigue attributed to CLL\r\n** Fevers >= 100.5 degree Fahrenheit (F) for 2 weeks without evidence of infection\r\n** Drenching night sweats without evidence of infection\r\n* Evidence of progressive bone marrow failure with hemoglobin =< 11 g/dL or platelet count =< 100 x 10^9/L\r\n* Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly\r\n* Note: marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient for protocol therapy OR\r\nbiopsy proven Richter’s transformation or Hodgkin transformation of the CLL; NOTE: both untreated and previously treated patients in this category can be enrolled; they do not need to meet the progressive disease criteria in first bullet as long as measurable disease can be detected by positron emission tomography (PET)/computed tomography (CT) or CT (>= 1.5 cm in diameter)
CLL WITH RICHTER's TRANSFORMATION (ARM C) ONLY
CLL ARMS (ARM A and ARM C) FOR COMBINATION THERAPY INCLUDING IBRUTINIB or IDELALISIB:
A histologically confirmed diagnosis of CLL/SLL/B-cell PLL according the International Workshop on CLL/SLL/B-cell PLL or variant of these (International Workshop on CLL [IWCLL] or World Health Organization [WHO] Criteria) and meet criteria for treatment or have need for cytoreduction for stem cell transplantation or alternative cell therapy; OR
Patients who have had prior (within 8 weeks of initiation of UC-961) or concurrent antibody therapy directed against CLL (i.e., Rituxan® and Campath®)
Group B: CD19+ B cell chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) undergoing allogeneic HSCT
Diagnosis of CLL by 2008 IWCLL criteria and with Rai stage intermediate or high risk CLL. Cohort 8 patients must have a diagnosis of PTCL.
Subjects must be diagnosed with CLL/SLL (chronic lymphocytic leukemia/small lymphocytic lymphoma) based on the standard histologic and immunophenotypic criteria described in the World Health Organization (WHO) classification of lymphoid malignancies, including immunophenotypic confirmation that the tumor cells co-express B cell antigens cluster of differentiation (CD)19/20 and CD5; mantle cell lymphoma should be excluded based on positive staining of the tumor cells for CD23, or the absence of staining of the tumor cells for cyclin D1 or the absence of t(11;14); this diagnosis should be confirmed at a Dana-Farber Harvard Cancer Center institution (Dana-Farber Cancer Institute [DFCI], Brigham and Women's Hospital [BWH], Massachusetts General Hospital [MGH], Beth Israel Deaconess Medical Center [BIDMC]) within approximately one month after the subject is registered; any question on histology confirmation should be brought to the attention of the Principal Investigator
Subjects must require treatment based on International Workshop on CLL (IWCLL) 2008 criteria
Inclusion Criteria:\n\n        To be eligible for inclusion in the primary escalation and expansion cohort 1 in this\n        study, patients must meet all of the following criteria:\n\n          1. Age 18 years or older\n\n          2. Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL):\n\n               1. History of histologically documented CLL or SLL that meets IWCLL diagnostic\n                  criteria according to the 2008 guidelines, and\n\n               2. Indication for treatment as defined by the 2008 IWCLL guidelines, or the need for\n                  disease reduction prior to allogeneic transplantation\n\n        Exclusion Criteria:\n\n        Patients who meet any of the following criteria are not eligible for the primary escalation\n        and expansion cohorts of this study:\n\n          1. Current or past transformation of CLL/SLL to prolymphocytic leukemia (PLL),\n             non-Hodgkin lymphoma, or Hodgkin lymphoma aggressive lymphoma outlined in the\n             inclusion criteria for the optional cohort.\n\n          2. Active and uncontrolled autoimmune cytopenia(s)\n\n          3. Any of the following prior therapies within 14 days prior to cycle 1, day 1:\n\n               1. Major surgery\n\n               2. Corticosteroids greater than 20 mg / day prednisone (or equivalent), unless used\n                  by inhalation or topical route, or unless necessary for premedication before\n                  iodinated contrast dye, or for autoimmune hemolytic anemia\n\n               3. Cytotoxic chemotherapy or biologic therapy, excepting BCR pathway kinase\n                  inhibitors for which no wash out is required (but must be stopped before cycle 1\n                  day 1)
Patient must have diagnosis of CLL that meets published 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute–sponsored Working Group (NCI-WG) criteria
Must have histologically or flow cytometry confirmed diagnosis of B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) according to National Cancer Institute Working Group (NCI-WG) 1996 guidelines; the malignant B cells must co-express CD5 with CD19 or CD20; patients who lack CD23 expression on their leukemia cells should be examined for (and found NOT to have) either t(11;14) or cyclin D1 overexpression, to rule out mantle cell lymphoma; patients with CLL who have progressed on prior ibrutinib therapy will be eligible; patients with B-cell prolymphocytic leukemia and patients with Richter’s transformation of CLL/SLL are NOT eligible
Diagnosis of chronic lymphocytic leukemia (CLL) meeting criteria established in the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for the diagnosis and treatment of CLL
Other concurrent low-grade malignancies such as CLL (Rai 0) may be considered after discussion and permission from Sponsor
Clinical and phenotypic verification of B cell CLL or SLL and measurable disease. Immunophenotyping of the leukemic cells (blood, lymph node, or bone marrow) must demonstrate a monoclonal (or light chain positive) B cell population with immunophenotype consistent with CLL (e.g.: co-expressing CD19, CD5, and CD23)
Adequate hematologic function (platelet and absolute neutrophil count [ANC] values in accordance with ongoing ibrutinib studies for patients with CLL), unless cytopenias are due to bone marrow highly infiltrated with CLL cells, e.g. > 80%
Histological diagnosis of CLL/SLL or MCL as documented in medical records.
Diagnosis of CLL per the WHO classification
Evidence of at least one measurable lesion on imaging with the following exceptions\r\n* Patients treated with interim chemotherapy for disease control between enrollment and ET190L1-ARTEMIS T cell infusion who do not have measurable disease at re-screening are still eligible\r\n* CLL/SLL with documented B-cell absolute lymphocytosis > 5 x 10^9 cells/L peripheral blood or infiltration of lymph nodes and/or bone marrow infiltration by CLL phenotype cells defined as clonal B cells with majority population co-expressing CD5 and CD19, with surface immunoglobulin (sIg, kappa or lambda but not both) and CD20 (dim), CD23+ (if CD20 or sIg are bright or if CD23 is dim or negative [atypical CLL phenotype] then fluorescence in situ hybridization (FISH) for 11:14 translocation must be performed to differentiate from mantle cell lymphoma)\r\n* Lesions previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy\r\n** Measurable lesions are nodes/nodal masses > 1.5 cm, extranodal masses > 1.0 cm or positron emission tomography (PET) avid lesions consistent with lymphoma
For patients with Richter’s transformation, one prior line of therapy for either CLL or Richter’s transformation (RT) is required
Ages =< 50 years with chronic lymphocytic leukemia (CLL)
CLL–must have either 1) failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (FLU) (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); 2) failed FLU-cyclophosphamide (CY)-rituximab (FCR) combination chemotherapy at any time point; or 3) have “17p deletion” cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR; or 4) patients with a diagnosis of CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL; 5) patients failing to achieve a response to ibrutinib as first-line therapy; 6) patients not responding to ibrutinib, idelalisib, or venetoclax as salvage therapy or intolerant of these agents as salvage therapy due to side effects; all CLL patients must have received prior myelosuppressive chemotherapy
No treatment indication according to IWCLL/NCI-WG (International Working Group in Chronic Lymphocytic Leukemia/National Cancer Institute-Working Group) 2008 criteria.
Diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that meets IWCLL diagnostic criteria.
Have measurable disease based on:\r\n* Lugano classification (cohorts A, C)\r\n* International Workshop on CLL (cohorts B, D)
Patients must have received at least 12 months of ibrutinib therapy and have measurable CLL by at least one of the following: Absolute monoclonal lymphocyte count > 4000/microL; OR measurable lymph nodes with at least one node > 1.5 cm in diameter on CT; OR bone marrow with >= 30% lymphocytes on aspirate differential; OR detectable CLL cells using a standardized flow cytometry assay for minimal residual disease
Absolute neutrophil count (ANC) >= 500/ul in the absence of growth factor support unless due to compromised bone marrow production from CLL, indicated by >= 80% CLL in marrow
Received other investigational therapeutic agent for CLL/SLL within 21 days of starting venetoclax
Patients with previously treated CLL and biopsy-proven Richter’s transformation with diffuse large B-cell lymphoma (DLBCL) histology according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria (Richter Transformation - RT) and CD19 positive by flow cytometry OR immunohistochemistry.
Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) meeting International Workshop on Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute (NCI)-Working Group (WG) criteria, and relapsed after or refractory to at least 1 prior treatment
Subjects must be diagnosed with CLL/SLL and do not meet the IWCLL criteria for treatment
Patients whose expected time to CLL/SLL treatment, according to our nomogram posted on the leukemia protocol priority list, is two years or less
Phase I portion of the study: Histologically or flow cytometry confirmed diagnosis of B-CLL/SLL according to National Cancer Institute (NCI)-Working Group (WG) 1996 guidelines
Patients with chemo-sensitive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with persistent or recurrent disease after fludarabine-based regimens with < 25% involvement by CLL/SLL cells
Part 2 (Cohort Expansion): Diagnosis of DLBCL, FL, MCL, HL, CLL/SLL, ALL, MM, or AML as documented in medical records.
Patients will have a diagnosis of CLL or small lymphocytic lymphoma (SLL) who meet one or more criteria for active disease as defined by the International Working Group for CLL (IWCLL) and are: a) cohort 1: refractory to or relapsed after at least one prior therapy; or b) cohort 2: untreated patients with high-risk molecular features such as del(17p), mutated TP53, del(11q), unmutated IGHV gene, or are > 65 years of age; or cohort 3: patients with CLL who have been on ibrutinib for at least 12 months with a partial response
Patients with a diagnosis of CLL/SLL who are refractory to and/or relapsed after at least one prior therapy will be eligible (cohort 1); untreated patients with high-risk features (del(17p), or mutated TP53, or del(11q), or unmutated immunoglobulin heavy chain variable [IGHV], or >= 65 years of age) are eligible (cohort 2) provided they have active disease requiring treatment as defined by the International Working Group for CLL (IWCLL)
Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following a minimum of two lines of standard therapy
Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL), confirmed by flow cytometry and as per the criteria outlined by the IWCLL/Hallek December 2008
Documented CD19+ chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
CLL patients with known or suspected transformed disease (i.e. Richter’s transformation)\r\n* Note: biopsy proven absence of transformation is not required
Patients with a diagnosis of CLL/small lymphocytic lymphoma (SLL), with mutated (> 2% deviation from germ line) IGHV gene, who meet criteria to initiate first-line treatment per International Workshop on CLL Working Group (IWCLL) 2008 guidelines
Patients must not have received prior CLL-directed therapy
Histologically or cytologically confirmed Hodgkin and all NHL subtypes excluding Burkitt, chronic lymphocytic leukemia (CLL) and lymphoblastic lymphoma that is considered to have relapsed or to be refractory to primary chemotherapy
Patients with CLL, Burkitt or lymphoblastic lymphoma are excluded
Clinically significant and ongoing immune suppression including, but not limited to, systemic immunosuppressive agents such as cyclosporine or corticosteroids, chronic lymphocytic leukemia (CLL), uncontrolled human immunodeficiency virus (HIV) infection, or solid organ transplantation
Participants with a diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Must have a confirmed diagnosis of CLL defined by 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
Must have received one prior therapy for CLL
Participants with CLL or DLBCL who have Richter's Transformation
Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma
Patients will have a diagnosis of CLL or small lymphocytic lymphoma (SLL), refractory to or relapsed after at least one prior standard therapy or untreated with deletion (del)(17p) by fluorescence in-situ hybridization (FISH) (high-risk cytogenetics) and have an indication for treatment by IWCLL 2008 criteria (Cohort 1) OR have been on ibrutinib for at least 9 months with measurable persistent disease (absolute lymphocyte count [ALC] > 4 K/muL, any lymph node > 1.5 cm by computed tomography [CT] scan, or > 30% lymphocytes on bone marrow aspirate differential) (Cohort 2), OR patients will have a diagnosis of RT, refractory to and/or relapsed after at least one prior standard therapy or untreated with del(17p) by FISH (high-risk cytogenetics) (Cohort 3)
Small lymphocytic lymphoma(SLL) with absolute lymphocyte count <5x10*9/L at study entry
B-cell (B)-chronic lymphocytic Leukemia (CLL)\r\n* Relapse/progression after two previous regimens\r\n* No response or progression =< 6 months after fludarabine (fludarabine phosphate) or bendamustine based regimen\r\n* Progression within 24 months of a fludarabine and alkylator combination regimen\r\n* Progression after any regimen in the presence of deletion (del)17p or mutated tumor protein p53 (TP53)\r\n* Persons with high grade lymphoma transformation
Diagnosis of CLL: monoclonal B-cells co-expressing >= one B-cell marker (cluster of differentiation [CD]19, CD20, or CD23) and CD5 in peripheral blood or lymph node
Indication for treatment as defined by the International Workshop in Chronic Lymphocytic Leukemia (IWCLL) Guidelines
No previous treatment for CLL
Have documented chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) according to National Cancer Institute (NCI) criteria
Confirmed B-cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and other B-cell lymphoproliferative disorders as approved by the Medical Monitor or Study Chair
Patients with small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) are excluded during the phase I portion of the study
Patients must have histologically confirmed B cell CLL (B-CLL) with low or intermediate risk disease as defined by the modified Rai criteria
Patients who meet any of the National Cancer Institute (NCI) Working Group criteria to initiate treatment for CLL are NOT eligible for participation
Patients who have had any prior treatment for CLL, including chemotherapy, corticosteroids, biologic therapy, or immunotherapy are NOT eligible for participation
Histologically confirmed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
Patients with active chronic lymphocytic leukemia (CLL) disease requiring urgent chemotherapy
Patients less than 30 days from last treatment for CLL
Each patient with CLL/SLL must meet all of the following inclusion criteria to be enrolled on the study:
Patients must have met the diagnostic criteria for CLL/SLL according to the IWCLL 2008 [13] or WHO Guidelines at some point during their disease course:
Patients with SLL: tumor biopsy immunohistochemistry diagnostic of SLL or blood/bone marrow immunophenotype similar to CLL without lymphocytosis and enlarged lymph nodes.
Patient must have relapsed or refractory CLL/SLL following at least one purine analog-containing regimen (or after one non-purine analog containing regimen if there is a relative contraindication to purine-analog containing therapy) and not have traditional options available or decline these. Patients with prolymphocytic leukemia (PLL)-CLL or PLL transformation of CLL are eligible.
Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma as per IW-CLL 2008 criteria; specifically, patients must also require therapy for that diagnosis, based on meeting at least one of the following criteria:\r\n* Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 11.0 g/L) and/or thrombocytopenia (platelets < 100 x 10^9/L)\r\n* Massive (>= 6 cm below the left costal margin), progressive, or symptomatic splenomegaly\r\n* Massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy\r\n* Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of < 6 months; lymphocyte doubling time may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months; in subjects with initial blood lymphocyte counts of < 30 x 10^9/L, LDT should not be used as a single parameter to define indication for treatment; in addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded \r\n* Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy \r\n* Documented constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs:\r\n** Unintentional weight loss > 10% within 6 months prior to screening\r\n** Significant fatigue (inability to work or perform usual activities)\r\n** Fevers > 100.5° Fahrenheit (F) or 38.0° Celsius (C) for 2 or more weeks prior to screening without evidence of infection\r\n** Night sweats for more than 1 month prior to screening without evidence of infection
No prior CLL-directed therapy that was instituted due to patient previously meeting IWCLL 2008 criteria for treatment
Patients with CLL, SLL, or prolymphocytic leukemia must have < 20% bone marrow involvement by malignancy (to lower risk of graft rejection)
ALL/CLL in 1st remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL >= 2nd remission
CLL: \r\n* Patients with either a:\r\n** Diagnosis of T-cell CLL or T-cell prolymphocytic leukemia (PLL) who have failed initial chemotherapy, patients with T cell CLL or PLL or \r\n** Diagnosis of B-cell CLL, B-cell small lymphocytic lymphoma, or B-cell CLL that progressed to PLL who either:\r\na) Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-chlorodeoxyadenosine [CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)\r\nb) Failed any aggressive chemotherapy regimen, such as fludarabine, cyclophosphamide and rituximab (FCR), at any time point\r\nc) Have \17p deletion\ cytogenetic abnormality and relapsed at any time point after initial chemotherapy\r\n* Harvesting criteria for autologous HCT: \r\n** Previously collected PBMC may be used\r\n** Circulating CLL cells < 5000\r\n* Marrow involvement with CLL cells < 50%
Diagnosis of B-CLL, confirmed by flow cytometric analysis and as per the criteria outlined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL)/Hallek December 2008
Any prior therapy for B-CLL must have been discontinued >= 28-days prior to registration
Patient must require treatment for symptomatic B-CLL as defined by the by the IWCLL/Hallek, December 2008 criterion or as determined clinically necessary by the treating physician
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Must be refractory to fludarabine (fludarabine phosphate) or fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)
Previous treatment for CLL with chemotherapy or monoclonal antibodies
CLL patients with active transformed disease (Richter’s transformation) are ineligible for enrollment on this study
Known histological transformation from CLL to an aggressive lymphoma (Richter's)
A diagnosis of CLL as defined by IWCLL 2008 criteria and currently on treatment with ibrutinib for at least 18 months with residual disease and without evidence of disease progression.
A diagnosis of CLL as defined by IWCLL 2008 criteria and currently on treatment with ibrutinib without evidence of disease progression.
Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following standard therapy; patients with progressive CLL following standard therapy who meet European Bone Marrow Transplant (EBMT) consensus guidelines of indications for allogeneic stem cell transplantation; this includes patients with (1) lack of response or early relapse within 1 year of receiving a purine analog-containing treatment regimen, (2) disease relapse within 2 years of receiving a purine analog combination therapy or after other therapies such as autologous stem cell transplantation, and (3) CLL associated with tumor protein (p)53 mutations or deletions and/or deletion (del) (17p) requiring therapy; patients must have chemosensitive disease with at least a partial response (PR) or stable disease (SD) with last treatment regimen
Patients must have a confirmed diagnosis of CLL as defined by the International Workshop on CLL 2008 (iwCLL2008) criteria below:\r\n* Presence of at least 5 x 10^9 B lymphocytes/L (5000/uL) in the peripheral blood\r\n* Morphologically, the lymphocytes must appear of small to moderate size with < 55% prolymphocytes, atypical lymphocytes or lymphoblasts\r\n* The clonality and immunophenotype of the circulating B-lymphocytes must be confirmed by flow cytometry to express cluster of differentiation (CD)5, CD23, CD19, CD20, CD52 and either kappa or lambda light chain
Diagnosis of active CLL or SLL that meets at least 1 of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment
Use of any anticancer medication from documented PD on Study IPI-145-07 to enrollment (Note: corticosteroids to manage CLL/SLL-related symptoms are allowed)
Diagnosis of chronic lymphocytic leukemia (CLL) meeting criteria established in the World Health Organization (WHO) classification of hematologic disorders or International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
Any previous treatment (chemotherapy, radiotherapy, and/or monoclonal antibodies) intended specifically to treat CLL
Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with active disease defined by presence of > 5% malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins, and/or positive imaging for extramedullary disease. Patients must have measurable disease at time of study treatment.
Diagnosis of:\r\n* Biopsy-proven small lymphocytic lymphoma (SLL) , or\r\n* Diagnosis of chronic lymphocytic leukemia (CLL) with a clonal B-cell population in the peripheral blood with immunophenotyping consistent with CLL as follows:\r\n** The population of lymphocytes share both B-cell antigens (CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)\r\n** Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. IGHV analysis)\r\n** Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH/CCND1)
Patients must be previously untreated\r\n* Note: Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL or SLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments or supplemental vitamins) will not be considered “prior treatment”; prior corticosteroid therapy for an indication other than CLL/SLL will not be considered “prior treatment”
Date of CLL/SLL diagnosis ? 24 months prior to registration
Expansion cohort - histologically or flow cytometry confirmed diagnosis of B-CLL/SLL according to NCI-WG 1996 guidelines; patients who lack CD23 expression on their leukemia cells should be examined for (and found NOT to have) either t(11;14) or cyclin D1 overexpression, to rule out mantle cell lymphoma
Patients with CLL/SLL demonstrate active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment:\r\n* A minimum of any one of the following constitutional symptoms:\r\n** Unintentional weight loss > 10% within the previous 6 months prior to screening\r\n** Extreme fatigue (unable to work or perform usual activities)\r\n** Fevers of greater than 100.5 F for >= 2 weeks without evidence of infection\r\n** Night sweats without evidence of infection\r\n* Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia\r\n* Massive (i.e., > 6 cm below the left costal margin), progressive or symptomatic splenomegaly\r\n* Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive lymphadenopathy\r\n* Progressive lymphocytosis with an increase of > 50% over a 2-month period, or an anticipated doubling time of less than 6 months\r\n* Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids\r\n* Patients with NHL and with B-cell prolymphocytic leukemia must have an indication for treatment in the opinion of the investigator
Histological confirmation of relapsed/refractory B-cell NHL, CD20+ \r\n* NOTE: patients with small lymphocytic lymphoma (SLL) are eligible however patients with chronic lymphocytic leukemia (CLL) are not eligible\r\n* Waldenstrom macroglobulinemia patients are not eligible; aggressive lymphoma patients who are transplant eligible must have undergone a transplant\r\n* The biopsy confirming relapse can be up to 24 weeks prior to registration as long as there is no intervening therapy
Known immunosuppressive disease, for example HIV infection or history of bone marrow transplant or chronic lymphocytic leukemia (CLL).
Patients must have histologically or flow cytometry confirmed diagnosis of B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) according to the IWCLL 2008 criteria. The malignant B cells must co-express CD5 with CD19 or CD20. Patients who lack CD23 expression on their leukemia cells should be examined for (and found NOT to have) either t(11;14) or cyclin D1 overexpression, to rule out mantle cell lymphoma.
Patients with relapsed/refractory CLL defined as having received ?2 treatment regimens that included:
A disease expert at the study site must have a detailed discussion with the patient of other treatment options which either have been approved by the FDA or are part of or relevant to the standard care of patients with B-CLL/SLL in the multiply relapsed setting
FOR PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL):
Diagnosis of CLL without the following: Richter's transformation, prolymphocytic leukemia (PLL), small lymphocytic lymphoma (SLL)
FOR PATIENTS WITH MM OR CLL:
Pathologic diagnosis per local institutional review of Richter syndrome that transformed from chronic lymphocytic leukemia (CLL).
Diagnosis of CLL.
Diagnosis of CD20+ CLL.
Any prior systemic treatment for CLL.
Chronic lymphocytic leukemia/small lymphocytic lymphoma (SLL)
Known histological transformation from iNHL or CLL to an aggressive form of non-Hodgkin lymphoma (ie, Richter transformation) except if the CLL patient is enrolling in the B-cell receptor (BCR) previously treated cohort
Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria (Hallek 2008), with active disease meeting at least 1 IWCLL criteria for requiring treatment.
Any prior therapy used for treatment of CLL/SLL
Diagnosis of Chronic Lymphocytic Leukemia (CLL) established according to International Workshop Chronic Lymphocytic Leukemia (IWCLL) criteria.
Relapsed or refractory CLL pre-treated with at least one prior line of systemic therapy for CLL.
Known transformation of Chronic Lymphocytic Leukemia (CLL) to an aggressive B-cell malignancy at the time of screening
Previous CLL treatment with a CD37-targeting antibody or a CD37-antibody drug conjugate.
Prior diagnosis of CLL
Must have received ? 1 prior therapy for CLL
Treatment with systemic anticancer therapy for CLL is prohibited between discontinuation of ibrutinib and enrollment on this trial.
Known immunosuppressive disease, for example HIV infection or history of bone marrow transplant or chronic lymphocytic leukemia (CLL)
Treatment naïve or previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; previously treated, pathologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that requires as per the National Cancer Institute (NCI) Working Group Guidelines for the treatment of CLL; the diagnosis of CLL is defined by the presence of 5 x 10^9 clonal B-lymphocytes/L in the peripheral blood; clonality of the lymphocyte population is established with flow cytometry and the demonstration of the following surface markers: CD5, CD23, CD19, CD20 and the presence of either kappa or lambda immunoglobulins; the diagnosis of SLL may be made with the demonstration of < 5 x 10^9 clonal B-lymphocytes/L in the peripheral blood, with the clinical or radiographic features of enlarged lymph nodes or organomegaly, and the demonstration of SLL cells in the lymph node biopsy; institutional flow cytometry or immunohistochemistry must confirm CD20 antigen expression; patients may not have had a history of Richter’s transformation
Subject who has high-risk chronic lymphocytic leukemia/small lymphocytic lymphoma.
Confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL)
Relapsed, refractory or previously untreated CLL
CLL requiring treatment; patients must be eligible for ibrutinib therapy
Patients must have histologically identified chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) as defined by the World Health Organization (WHO) classification of hematopoietic neoplasms
No prior therapy for CLL/SLL, including chemotherapy and/or radiotherapy is allowed
Patients who have had any treatment for their CLL/SLL, including but not limited to chemotherapy, radiotherapy, or immunotherapy, prior to entering the study
Patients must have a diagnosis of CLL/small lymphocytic lymphoma (SLL) or prolymphocytic leukemia (PLL) and be previously treated; given the poor outcome of CLL/SLL/PLL patients with 17p deletion (del) or tumor protein (TP)53 mutation to standard frontline chemo-immunotherapy, such patients will be eligible if they are untreated
Patients must have an indication for treatment by 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
Patients must be diagnosed with CLL in accordance with International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that includes all of the following:\r\n* >= 5 x 10^9 B lymphocytes (5000/uL) in the peripheral blood\r\n* On morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes\r\n* CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of cluster of differentiation (CD)19 and CD20, as well as the T-cell antigen CD5; patients with bright surface immunoglobulin expression or lack of CD23 expression in > 10% of cells must lack t(11;14) translocation by interphase cytogenetics
Prior treatment\r\n* Patients must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids)\r\n* Treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment; palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration
Diagnosis of relapsing/refractory or previously untreated CLL
Clinical and phenotypic verification of B cell chronic lymphocytic leukemia (CLL) and measurable disease; immunophenotyping of the leukemic cells (blood or marrow) must demonstrate a monoclonal (or light chain positive) B cell population with immunophenotype consistent with CLL (e.g., co-expressing CD19 and CD5)
Patients with a diagnosis of CLL (any stage) with absolute lymphocyte count (ALC) >= 20 x 109/l, requiring therapy
Participants must have confirmed CLL/small lymphocytic lymphoma (SLL) relapsed after at least one prior therapy and currently in need of treatment by IWCLL 2008 criteria
All patients must have a diagnosis of chronic lymphocytic leukemia (CLL) by immunophenotyping and flow cytometry analysis of blood or bone marrow\r\n* Patients must meet criteria for treatment based on the criteria proposed by National Cancer Institute (NCI)-sponsored CLL Working Group to include at least one of the following:\r\n** Weight loss of more than 10% over the preceding 6 months; or\r\n** Extreme fatigue attributable to progressive disease; or\r\n** Fever or night sweats without evidence of infection; or\r\n** Worsening anemia (Rai stage Ill) or thrombocytopenia (Rai stage IV); or\r\n** Massive lymphadenopathy (> 10 cm) or rapidly progressive lymphocytosis (lymphocyte doubling time < 6 months); or \r\n** Prolymphocytic or Richter's transformation; or\r\n* Patients with CLL who have received at least one prior line of therapy; or\r\n* Patients with CLL who have frequent infections and/or recurrent secondary cancers
Patients will have a diagnosis of CLL or small lymphocytic lymphoma (SLL) who meet one or more criteria for active disease as defined by the International Working Group for CLL (IWCLL) and are: a. Cohort 1: refractory to and/or relapsed after at least one prior therapy OR b. Cohort 2: untreated patients with high-risk molecular features such as del(17p), mutated TP53, del(11q), unmutated IGHV gene, or are > 65 years of age
Treatment-naïve CLL patients must meet the following requirements (Phase II only):\r\n* Symptomatic disease as defined by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria\r\n* Received no prior chemotherapy, immunotherapy, or targeted therapy for the treatment of CLL with the exceptions of palliative loco-regional radiotherapy and corticosteroids for symptom control
Clinically significant and ongoing immune suppression including, but not limited to, systemic immunosuppressive agents such as cyclosporine or corticosteroids, chronic lymphocytic leukemia (CLL), uncontrolled human immunodeficiency virus (HIV) infection, or solid organ transplantation
Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 10*9/L at the time of diagnosis and at study entry.
Chronic lymphocytic leukemia (CLL).
Histologically confirmed B-cell non-Hodgkin lymphoma (B-NHL), Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Cohort B-1: SLL/CLL: 1) Deletion of short arm of chromosome 17 or 11 q based on institutional assessment 2) Relapsed/refractory after at least 1 prior systemic therapy 3) Active disease based in IWCLL criteria
Cohort B-4: 1) Histologically-confirmed Richter syndrome defined as transformation of CLL or SLL into an aggressive lymphoma 2) Previously treated with at least one line of standard, systemic chemotherapy or not eligible for standard therapy 3) At least 1 measurable site of disease based on the Revised Response Criteria for Malignant Lymphoma
Previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment
Confirmed diagnosis of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), or small lymphocytic lymphoma (SLL)
CLL/SLL patients must have:\r\n* Indication for treatment according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria\r\n* Received at least one prior standard treatment regimen
Documented previously untreated CLL according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
CLL requiring treatment according to IWCLL criteria
Transformation of CLL to aggressive Non-Hodgkin's lymphoma (Richter's transformation or pro-lymphocytic leukemia)
Diagnosis of CLL including:\r\n* Monoclonal B-cells co-expressing >= one B-cell marker (cluster of differentiation [CD]19, CD20, or CD23) and CD5 in peripheral blood or lymph node
Must have a confirmed diagnosis of CLL and an indication for treatment as per IW-CLL 2008 criteria
No prior therapy for CLL due to the patient’s meeting IW-CLL 2008 criteria for treatment
Men and women ? 18 years of age with a confirmed diagnosis of CLL, which has relapsed after, or been refractory to, ? 1 previous treatments for CLL; however, subjects with 17p deletion are eligible if they have relapsed after, or been refractory to, 1 prior treatment for CLL.
Subject must have a diagnosis of CLL that meets 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (iwCLL NCI-WG) criteria
Subjects must have CLL/SLL, as documented by a history at some point in time of an absolute peripheral blood B cell count > 5000/ul, with a monoclonal B cell population co-expressing cluster of differentiation (CD)19, CD5, and CD23, or if CD23 negative, then documentation of the absence of t(11;14) or cyclin D1 overexpression; alternatively patients with lymphadenopathy in the absence of circulating disease will also be eligible for this study if lymph node biopsy or bone marrow biopsy establishes the diagnosis of CLL with the above immunophenotype
Subjects must not have received any prior systemic therapy for CLL and currently have an indication for treatment as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 guidelines:\r\n* Massive or progressive splenomegaly; OR\r\n* Massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR\r\n* Grade 2 or 3 fatigue; OR\r\n* Fever >= 100.5 degrees Fahrenheit or night sweats for greater than 2 weeks without documented infection; OR\r\n* Presence of weight loss >= 10% over the preceding 6 months; OR\r\n* Progressive lymphocytosis with an increase of >= 50% over a 2-month period or an anticipated doubling time of less than 6 months; OR\r\n* Evidence of progressive marrow failure as manifested by the development of or worsening of anemia and or thrombocytopenia
Patients must have not received any prior treatment for CLL or SLL
Any indication to start treatment for CLL based on NCI-WG criteria
Prior therapy for CLL/SLL
Diagnosis of CLL according to the National Cancer Institute (NCI)/Internal Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria; this includes previous documentation of:\r\n* Biopsy-proven small lymphocytic lymphoma or\r\n* Diagnosis of CLL according to the NCI/IWCLL criteria as evidenced by all of the following:\r\n** Peripheral blood lymphocyte count of greater than 5 x 10^9/L\r\n** Immunophenotype consistent with CLL defined as:\r\n*** The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc)\r\n*** Clonality as evidenced by kappa or lambda light chain restriction (typically dim immunoglobulin expression)\r\n* Negative FISH analysis for t(11;14)(immunoglobulin heavy locus [IgH]/cyclin D1 [CCND1]) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g. marrow aspirate or lymph node biopsy)
Men and women ? 18 years of age with a confirmed diagnosis of CLL/SLL, which has relapsed after, or been refractory to, ? 2 previous treatments for CLL/SLL; however, subjects with 17p deletion are eligible if they have relapsed after, or been refractory to, 1 prior treatment for CLL/SLL.
Subjects have been diagnosed with measurable CLL/SLL.
Diagnosis of CLL per diagnostic criteria for relapsed or refractory CLL per the international workshop on chronic lymphocytic leukemia (iwCLL) guidelines
Transformation of CLL to aggressive non-Hodgkin lymphoma or central nervous system (CNS) involvement by CLL
Diagnosis of active CLL or SLL that meets at least one of the IWCLL 2008 criteria for requiring treatment (Binet Stage ? B and/or Rai Stage ? I)
Disease that has progressed during or relapsed after at least one previous CLL/SLL therapy
CLL with an indication for treatment based on iwCLL guidelines and clinical measurable disease, or
Subjects with CLL or SLL and high-risk features must have failed at least 2 lines of prior therapy, including a BTKi.
Subjects with CLL or SLL and standard-risk features must have failed at least 3 lines of prior therapy, including a BTKi.
Patients must have a diagnosis of CLL/SLL or B-cell prolymphocytic leukemia, as defined by the World Health Organization (WHO)
Documented CD19+ chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
Patients must have a pathological diagnosis of B-cell CLL
Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 109/L at the time of diagnosis and at study entry
Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease and chronic lymphocytic leukemia (CLL)
Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets protocol-defined criteria
Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy consisting of at least 2 cycles of a chemotherapy-containing regimen
Patients must have histologically or cytologically confirmed cluster of differentiation (CD)5 positive (+)/CD20+ B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma; the diagnosis of CLL is based upon the National Comprehensive Cancer Network (NCCN) guidelines; any outside pathology slides used as inclusion criteria for the patient will be reviewed at this institution to confirm the diagnosis; the patient must meet all of the following CLL criteria to participate in this study: \r\n* Absolute lymphocyte count > 5000/uL \r\n* CD20+ and CD5+ \r\n* Bone marrow lymphocytes >= 30% \r\n* Or previous confirmed diagnosis of CLL/SLL with less than 5000/ul or less than 30% lymphocytes in bone marrow (BM)
Patient has not received any prior treatment for CLL in the past
CLL patients with transformed disease (Richter's transformation) are ineligible for enrollment on this study
Patients must have a diagnosis of CLL/SLL and be previously treated
Diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL), previously untreated, Rai stage 0-ll
Patients with renal or liver dysfunction due to organ infiltration with CLL may be eligible after discussion with the study chairman
Presence of 2008 IWCLL/ NCI-WG indication for CLL treatment
Ages =< 50 years of age with chronic lymphocytic leukemia (CLL)
Previous treatment for CLL- including therapy with immunomodulatory agents Revlimid or thalidomide, regardless of response
Confirmed B-cell CLL/SLL with a characteristic immunophenotype by flow cytometry, and symptomatic disease requiring treatment
Must have a documented diagnosis of B-cell CLL.
Prior treatment for B-cell CLL.
Prior history of malignancies, other than CLL, unless the subject has been free of the disease for ?3 years. Exceptions include the following:
Must have a documented diagnosis of B-cell CLL (IWCLL guidelines for the diagnosis and treatment of chronic lymphocytic leukemia [Hallek, 2008]).
Systemic treatment for B-cell CLL in the interval between completing the last cycle of second-line induction therapy and randomization.
Prior history of malignancies, other than CLL, unless the subject has been free of the disease for ?5 years. Exceptions include the following:
More than 2 prior lines of CLL therapy.
Patients will have a diagnosis of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or cluster of differentiation (CD)20 positive low-grade lymphoproliferative disorder
confirmed CLL diagnosis and active CLL requiring treatment
not been treated for CLL before
prior CLL therapy
CLL transformation
B-chronic lymphocytic leukemia (CLL), small lympho(plasma)cytic lymphoma (B-SLL, B-LPL)\r\n* Relapse/progression after fludarabine (fludarabine phosphate) and at least one other salvage regimen or 2 standard regimens\r\n* If 17p deletion present, one standard regimen is sufficient
Prolymphocytic leukemia (PLL), T-cell chronic lymphocytic lymphoma (T-CLL)\r\n* T-PLL: treatment failure after Campath-1H and at least one other regimen\r\n* B-PLL: treatment failure after fludarabine and at least one other salvage regimen
For recipients with CLL or PLL, treatment failure for a specified therapy is defined as relapse within 6 months or failure to achieve remission \r\n* Recipients who are ineligible for a specified therapy (e.g., due to refractory cytopenias) may be considered for enrollment in this protocol\r\n* Recipients who have a 17p/p53 deletion who have never received fludarabine will be eligible\r\n* Recipients who have had Richter’s transformation who have not received prior chemotherapy for their CLL will be eligible
Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following standard therapy; or
Patients with a diagnosis of CLL (or SLL) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL)
Patients with lymphoma (non-Hodgkin lymphoma [NHL], chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL] or Hodgkin's lymphoma) with primary refractory or relapsed disease after standard chemotherapy at high risk of relapse with conventional autografting; patients with a diagnosis of CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL
Diagnosis of B-cell CLL, established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and having received at least 2 prior treatment regimens
CLL that warrants treatment
Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
Patients with diagnoses of CLL/SLL or non-Hodgkin lymphoma (NHL) patients, who meet the criteria of either relapse or progression at any time point after allogeneic HCT or those who experience persistent stable disease or persistent disease with regression between days 28 and 100 post-transplant using standard morphologic, flow cytometric, and/or imaging studies and following the disease response evaluation criteria established by the International Workshop on CLL (IWCLL) for CLL and those following Cheson 2007 criteria for NHL
Subjects must have a histopathologically confirmed diagnosis of an advanced non-hematologic malignancy or lymphoma or indolent NHL/CLL.
Diagnosis of B-cell CLL, with diagnosis established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
No prior therapy for CLL other than corticosteroids for disease complications.
CLL that warrants treatment
Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 10^9/L at the time of diagnosis
Histologically confirmed Richter's transformation (RT) from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Diagnosis of Chronic lymphocytic leukemia or Small lymphocytic lymphoma that meets at least one of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for treatment (Binet Stage ? B and/or Rai Stage ? I with symptoms)
Confirmed diagnosis of CLL or SLL based on IWCLL Criteria
Documented diagnosis of B-cell CLL, according to International Workshop on Chronic Lymphocytic Leukemia 2008
Presence of 17p deletion in CLL cells as demonstrated by fluorescence in-situ hybridization (FISH) testing
No prior therapy for CLL other than corticosteroids for disease complications
CLL that warrants treatment
Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
History of a non-CLL malignancy except for the following:
Clinically significant and ongoing immune suppression including, but not limited to, systemic immunosuppressive agents such as cyclosporine or corticosteroids, chronic lymphocytic leukemia (CLL), uncontrolled human immunodeficiency virus (HIV) infection, or solid organ transplantation
Patients with B-CLL (not in Richter’s transformation) with measurable disease
Manipulated B-CLL cells available (at least 6 injections)
Patients with relapsed chronic lymphocytic leukemia with high risk features: lack of objective response or relapse within 6 months following nucleoside-analogue based chemotherapy regimen or patients with 17p deletion CLL who lacked objective response to at least 1 preceding chemotherapy regimen
CIRS ? 6; 2. Creatinine Clearance < 70 mL/min; 3. Subject is not a candidate for a chemoimmunotherapy in the opinion of investigator. ii. Treatment with an approved BTK inhibitor is not required if subject has contraindications or is not a candidate for such a therapy in the opinion of the investigator. b. For Arm B, subjects with treatment-naïve or R/R CLL must meet the following criteria: i. Dose Escalation Phase: Subjects must not have received prior treatment with ibrutinib (or any other approved BTK inhibitors) and must have either R/R CLL or treatment naïve (ie, first-line) CLL if the subject:
is unfit for standard chemoimmunotherapy meeting at least 1 of the following co-morbidity criteria: a. CIRS ? 6; b. Creatinine Clearance < 70 mL/min; c. Subject is not a candidate for a chemoimmunotherapy in the opinion of the investigator. The reason for not being a candidate must be documented in CRF. ii. Dose Expansion Phase: Subjects must not have received prior treatment with ibrutinib (or any other approved BTK inhibitors) and must have high risk CLL. High risk is defined as: 1) 17p- and/or TP53 mutation positive in treatment naïve CLL; or 2) 17p- and/or TP53 mutation positive, and/or complex karyotype, and/or progression < 24 months after completion of 1st line chemoimmunotherapy in R/R CLL c. Subjects with R/R SLL or CLL with bulky disease (at least one lymph node measuring > 5.0 cm in diameter) are considered at higher risk for developing a TFR and may only be enrolled upon discussion with the sponsor's medical monitor and agreement to close medical management.
SLL / CLL SUBJECTS:
Diagnosis of B-cell CLL/SLL including:\r\n* Lymphocytosis of monoclonal B-cells co-expressing >= one B-cell marker (CD19, CD20, or CD23) and CD5 in peripheral blood or lymph node AND\r\n* Bone marrow with >= 30% mononuclear cells having the CLL/SLL phenotype
CLL and NHL Subjects:
Diagnosis of:\r\na) CLL according to the National Cancer Institute (NCI) criteria\r\nb) Small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria\r\nc) MBL according to the consensus criteria\r\n* This includes previous documentation of:\r\n** Biopsy-proven small lymphocytic lymphoma or\r\n** Diagnosis of CLL or MBL as evidenced by all of the following:\r\n*** Clonal B-cell population in the peripheral blood with immunophenotyping consistent with CLL defined as:\r\n**** The population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc)\r\n**** Clonality as evidenced by k (kappa) or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. immunoglobulin heavy chain variable [IGHV] analysis)\r\nNOTE: splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL \r\n*** Patients with a peripheral blood B-cell lymphocyte count of < 5 x 10^9/L and no evidence of lymphadenopathy or organomegaly will be classified as MBL; patients with a peripheral blood B-cell lymphocyte count of < 5 x 10^9/L who have evidence of lymphadenopathy will be classified as SLL; patients with a peripheral blood B-cell lymphocyte count >= 5 x 10^9/L will be considered to have CLL\r\n*** Before diagnosing MBL, CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH/cyclin D 1 [CCND1]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy
CLL or SLL patients only (does not apply to MBL patients): Rai stage 0-1 (both CLL and SLL patients can be staged using the Rai system)
Patients must be previously untreated and must NOT have any of the following indications for chemotherapy:\r\n* Evidence of progressive marrow failure as manifested by the development of or worsening anemia (=< 11 g/dL) and/or thrombocytopenia (=< 100 x 10^9/L) not due to autoimmune disease\r\n* Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly\r\n* One or more of the following disease-related symptoms:\r\n** Weight loss >= 10% within the previous 6 months\r\n** Extreme fatigue attributed to CLL\r\n** Fevers > 100.4 degree Fahrenheit (o^F) for 2 weeks without evidence of infection\r\n** Drenching night sweats without evidence of infection\r\nNote: 1) Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL or SLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments) will not be considered “prior treatment”\r\n2) Prior corticosteroid therapy for an indication other than CLL/SLL will not be considered “prior treatment”; previous use of corticosteroids for treatment of autoimmune complications of CLL/SLL does not constitute prior therapy for CLL/SLL
Biopsy confirmed, untreated, low-grade B-cell lymphoma, including follicular (Grade 1, 2, or 3A) [Harris, Swerdlow et al. 2008] or marginal, or CLL/SLL with lymph node involvement.
Small lymphocytic lymphoma (SLL) with absolute lymphocyte count
Confirmed diagnosis of CD20-positive CLL (per IWCLL guidelines, Hallek et al 2008)
Previously untreated CLL requiring treatment according to the IWCLL guidelines (Hallek et al 2008), as assessed by the investigator
Adequate baseline bone marrow function unless it due to underlying CLL disease No previous treatment for CLL by chemotherapy, radiotherapy, or immunotherapy
Patients must have histologically confirmed Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma.
For dose escalation monotherapy: CLL, HL, NHL, MM
For dose expansion monotherapy: CLL, HL, NHL
A diagnosis of CLL defined by a circulating B-lymphocyte count of greater than or equal to 5,000/uL at study entry or at any time in the past and flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, CD23, CD79b, and surface Ig prior to first dose of study treatment.
Subjects enrolled into the relapsed subject cohort must also meet the following criteria: Relapsed CLL: defined as a subject who has received at least one prior CLL therapy and previously achieved a complete or partial remission/response lasting at least 6 months.
Refractory CLL: defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months of the last anti-CLL therapy.
Known transformation of CLL (e.g. Richter's).
Known central nervous system involvement by CLL. Screening laboratory values: Platelets less than 100 x 109/L (unless due to CLL involvement of the bone marrow). Neutrophils less than 1.5 x 109/L (unless due to CLL involvement of the bone marrow). Serum creatinine greater than 1.5 times the upper limit of normal (ULN); subjects with a serum creatinine greater than 1.5 x ULN will be eligible if the calculated creatinine clearance [Cockcroft, 1976] is greater than or equal to 30 mL/min. Total bilirubin greater than 1.5 times ULN (unless due to liver involvement by CLL or Gilbert's disease). Transaminases greater than 2.5 times ULN.
Chronic lymphocytic leukemia (CLL)
Low-grade non-Hodgkin’s lymphoma or plasma cell neoplasm with either of the following, and with stable disease or better prior to transplantation:\r\n* Progressed during multiagent therapy, failed at least two prior therapies (excluding single agent rituximab), or there is evidence of prior transformation\r\n* Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) with 11q or 17p deletion or with progression < 6 months after a purine analog-containing regimen
For patients with SLL, CLL, or PLL, =< 20% of bone marrow cellularity involved by this process
Diagnosis of relapsed or refractory chronic lymphocytic leukaemia.
At least one criterion for active disease as defined by the International Workshop on CLL.
CLL, Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma. Subjects suspicious for transformation should undergo a biopsy to exclude the possibility of transformation. Subjects with a previous diagnosis of small lymphocytic leukemia (SLL) and a screening monoclonal B-lymphocyte count of ? 5000/µl are defined by 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria to have CLL; such patients are NOT eligible for this study.
Small lymphocytic lymphoma (SLL)
Patients with chemo-sensitive chronic lymphocytic leukemia (CLL) with persistent or recurrent disease after fludarabine-based regimens, no evidence of \bulky\ disease (> 10 cm in diameter)
Documented Cluster of Differentiation Antigen 20 (CD20) + B-Cell Chronic Lymphocytic Lymphoma (B-CLL)
Previously untreated Chronic Lymphocytic Leukemia (CLL) requiring treatment according to the National Cancer Institute (NCI) criteria
Prior CLL therapy
Patients will have a diagnosis of CLL or SLL who meet one or more criteria for active disease as defined by the International Working Group for CLL (IWCLL) and are relapsed and/or refractory after at least one prior therapy
PHASE I: Histological confirmation of relapsed (recurrent after previous therapy[ies]) or refractory (no response to previous therapy[ies]) B-cell NHL; note: patients with small lymphocytic lymphoma (SLL) are eligible however patients with chronic lymphocytic leukemia (CLL) are not eligible
Patients with B cell CLL/SLL who have active disease that meets 2008 International Workshop on CLL/National Cancer Institute-Working Group (IWCLL/NCI-WG) criteria to initiate treatment
Surface ROR1 expression by < 5% of CLL cells
Histologically or cytologically confirmed diagnosis of advanced non-Hodgkin lymphoma (NHL) of any histology (with the exception of participants with Waldenström macroglobulinemia [WM] and chronic lymphocytic leukemia [CLL]).
Inclusion Criteria MEI-401 Alone:\n\n          -  Diagnosis of relapsed/refractory CLL and/or relapsed/refractory SLL or FL\n\n          -  No prior therapy with PI3Kd inhibitors\n\n          -  No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was\n             intolerant of BTK therapy\n\n          -  Subject must have failed at least 1 prior systemic therapy\n\n          -  QT-interval corrected according to Fridericia's formula (QTcF) ? 450 milliseconds (ms)\n\n          -  Left ventricular ejection fraction >50%\n\n          -  For subjects, except those with CLL, must have at least one bi-dimensionally\n             measurable nodal lesion >1.5 cm, as defined by Lugano Classification\n\n          -  Willingness to participate in collection of pharmacokinetic samples\n\n          -  A negative serum pregnancy test within 14 days of study Day 0, for females of\n             childbearing potential\n\n        Inclusion Criteria ME-401 in Combination with Rituximab\n\n          -  Diagnosis of relapsed/refractory CLL SLL or FL, MZL, DLBCL and high-grade B-cell\n             lymphoma. Subjects must meet the following criteria for relapsed or refractory\n             disease:\n\n               1. Relapsed disease: a subject who previously achieved a CR or PR, but demonstrated\n                  disease progression after a response duration of >6 months\n\n               2. Refractory disease: a subject who demonstrated disease progression within 6\n                  months of most recent therapy\n\n          -  No prior therapy with PI3K? inhibitors\n\n          -  No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was\n             intolerant of BTK therapy\n\n          -  Subjects with CLL, SLL, FL, and MZL must have a failure of at least 1 prior systemic\n             therapy and be considered by the investigator a candidate for therapy with a\n             rituximab-based regimen; subjects with DLBCL and high-grade B-cell lymphoma must have\n             a failure of at least 2 prior therapies.\n\n          -  QT-interval corrected according to Fridericia's formula (QTcF) ?450 milliseconds (ms)\n\n          -  Left ventricular ejection fraction >50%\n\n          -  For subjects, except those with CLL, must have at least one bi-dimensionally\n             measurable nodal lesion >1.5 cm, as defined by Lugano Classification\n\n          -  Willingness to participate in collection of pharmacokinetic samples\n\n          -  A negative serum pregnancy test within 14 days of study Day 0 for females of\n             childbearing potential\n\n        Exclusion Criteria:\n\n          -  Known histological transformation from CLL to an aggressive lymphoma\n\n          -  Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia\n\n          -  Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B\n             core antibody\n\n          -  Positive for hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV)\n             antibody\n\n          -  Ongoing drug-induced pneumonitis\n\n          -  History of clinically significant cardiovascular abnormalities
Progression of CLL or MCL or FL or HD at time of transplant
Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) with 17p deletion, or with progression < 6 months after second or greater treatment regimen; must have the following to be an acceptable candidate as well:\r\n* =< 20% of bone marrow cellularity involved by SLL/CLL (to lower risk of graft rejection)\r\n* No lymph nodes >= 5 cm in any dimension\r\n* No massive splenomegaly, defined as > 6 cm below the left costal margin
Subjects must be diagnosed with CLL and do not meet the IWCLL criteria for treatment
Subjects must have discontinued all drugs used to treat CLL no later than day -30
Prior exposure to ABT-199 or B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL2) inhibitors
Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma as per International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) 2008 criteria; specifically, patients must also require therapy for that diagnosis, based on meeting at least one of the following criteria:\r\n* Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 11.0 g/L) and/or thrombocytopenia (platelets < 100 x 10^9/L)\r\n* Massive (>= 6 cm below the left costal margin), progressive, or symptomatic splenomegaly\r\n* Massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy\r\n* Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of < 6 months; lymphocyte doubling time may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months; in subjects with initial blood lymphocyte counts of < 30 x 10^9/L, LDT should not be used as a single parameter to define indication for treatment; in addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded\r\n* Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy\r\n* Documented constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs:\r\n** Unintentional weight loss > 10% within 6 months prior to screening\r\n** Significant fatigue (inability to work or perform usual activities) fevers > 100.5 degrees Fahrenheit (F) or 38.0 degrees Celsius (C) for 2 or more weeks prior to screening without evidence of infection\r\n** Night sweats for more than 1 month prior to screening without evidence of infection
Relapsed after or refractory to at least one prior CLL-directed therapy that was instituted due to patient previously meeting IWCLL 2008 criteria for treatment
Serum creatinine < 2.0 x ULN unless due to biopsy proven CLL kidney infiltration
Chronic lymphocytic leukemia (CLL) patients with IgG less than 500 mg/dl with/without symptoms who are either untreated or previously treated, regardless of response, at least 6 months from prior therapy (including monoclonal antibody [mAb])
PILOT III: CLL survivors
CLL\r\n* Absence of constitutional symptoms attributable to CLL\r\n* No lymph nodes > 1.5 cm in diameter on computed tomography\r\n* No hepatomegaly or splenomegaly by computed tomography\r\n* Absolute neutrophil count > 1500/microL\r\n* Platelet count > 100,000/microL\r\n* No clonal lymphocytes in the peripheral blood by immunophenotyping \r\n* Bone marrow with no evidence of clonal CLL (by flow cytometry and/or immunohistochemistry)
Chronic lymphocytic leukemia (CLL) – must have either:\r\n* Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine phosphate (FLU) (or another nucleoside analog) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog) \r\n* Failed FLU-cyclophosphamide (CY)-rituximab (FCR) combination chemotherapy at any time point; or \r\n* Have “17p deletion” cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR\r\n* Patients with a diagnosis of CLL (or small lymphocytic lymphoma) that progresses to prolymphocytic leukemia (PLL); or \r\n* Patients with T-cell CLL or PLL
Newly diagnosed aggressive lymphoma or CLL/small lymphocytic lymphoma (SLL) that meets disease specific criteria below:
Study 2 - CLL/SLL\r\n* Newly diagnosed (< 12 months from pre-registration on this study) CLL according to the National Cancer Institute (NCI) criteria or SLL according to the World Health Organization (WHO) criteria; this includes previous documentation of:\r\n** Biopsy-proven small lymphocytic lymphoma\r\n** Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following:\r\n*** Peripheral blood lymphocyte count of > 5,000/mm^3; if present, prolymphocytes should be < 55%\r\n*** Immunophenotyping consistent with CLL defined as:\r\n**** The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20, or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)\r\n**** Dim surface immunoglobulin expression\r\n**** Restricted surface kappa or lambda light chain expression\r\n*** Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescent in situ hybridization (FISH) analysis for t(11;14)(immunoglobulin H [IgH]/cyclin D 1 [CCND1]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy\r\n* Rai stage 0 or 1\r\n* Previously untreated\r\n* Asymptomatic with the plan for observation\r\n* Life expectancy of at least 24 months\r\n* Willing to provide tissue for correlative research purposes
Chronic lymphocytic leukemia (CLL).
Subject diagnosed with chronic lymphocytic leukaemia (CLL) who is receiving only oral cancer therapy (subject receiving intra-venous cancer therapy for CLL or intra-venous cancer therapy in combination with oral therapy may be enrolled).
Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma as per International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) 2008 criteria with biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), consistent with Richter’s Syndrome
Patients with the Hodgkin variant transformation of CLL will be excluded
Food and Drug Administration (FDA)-approved indications for idelalisib of relapsed, histologically confirmed B-cell indolent non-Hodgkin lymphoma (iNHL) or chronic lymphocytic leukemia (CLL)
Participant treats patients with CLL
Patient diagnosed with CLL < 60 days ago
Diagnosis of either Non-CLL B cell malignancy or CLL/SLL
Confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL)
Richter's transformation or CLL transformation to aggressive lymphoma
Clinical and phenotypic verification of B cell CLL or small lymphocytic lymphoma (SLL) and measurable disease; immunophenotyping of the leukemic cells (blood, lymph node, or bone marrow) must demonstrate a monoclonal (or light chain positive) B cell population with immunophenotype consistent with CLL (e.g.: co-expressing CD19, CD5, and CD23)
Platelet count >= 30,000/uL (platelet values in accordance with ongoing ibrutinib studies for patients with CLL), unless cytopenias are due to bone marrow highly infiltrated with CLL cells, e.g. > 80%; AND
Absolute neutrophil count >= 500 /uL (absolute neutrophile count [ANC] values in accordance with ongoing ibrutinib studies for patients with CLL), unless cytopenias are due to bone marrow highly infiltrated with CLL cells, e.g. > 80%