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
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
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).
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
ofatumumab (terminal half-life in CLL = 17.6 days); required washout = 88 days (13 weeks)
CLL/SLL PATIENTS (ARM A) ONLY
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
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®)
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 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)
Other concurrent low-grade malignancies such as CLL (Rai 0) may be considered after discussion and permission from Sponsor
Histological diagnosis of CLL/SLL or MCL as documented in medical records.
Diagnosis of CLL per the WHO classification
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
Received other investigational therapeutic agent for CLL/SLL within 21 days of starting venetoclax
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
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)
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
Must have received one prior therapy for CLL
No previous treatment for CLL
Patients must have histologically confirmed B cell CLL (B-CLL) with low or intermediate risk disease as defined by the modified Rai criteria
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:
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.
No prior CLL-directed therapy that was instituted due to patient previously meeting IWCLL 2008 criteria for treatment
Poor-risk CLL or SLL as follows: 11q deletion disease that has progressed after a combination chemotherapy regimen, 17p deletion disease, or histologic conversion; patients with transformed lymphomas must have stable disease or better
Patients with CLL, SLL, or prolymphocytic leukemia must have < 20% bone marrow involvement by malignancy (to lower risk of graft rejection)
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%
During phase I: all patients with relapsed disease will be eligible if they have received at least 1 prior standard CLL therapy and no more than 4 prior therapies (one of which must be a purine analog and/or an alkylating agent)
Previous treatment for CLL with chemotherapy or monoclonal antibodies
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
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)
Any previous treatment (chemotherapy, radiotherapy, and/or monoclonal antibodies) intended specifically to treat CLL
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
Received at least 2 prior therapies (regimens) for CLL
FOR PATIENTS WITH MM OR CLL:
Diagnosis of CLL.
Must have received ? 1 prior therapies for CLL.
Diagnosis of CD20+ CLL.
Any prior systemic treatment for CLL.
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
Relapsed or refractory CLL pre-treated with at least one prior line of systemic therapy for CLL.
Prior diagnosis of CLL
Must have received ? 1 prior therapy for CLL
No prior therapy for CLL/SLL, including chemotherapy and/or radiotherapy is allowed
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
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
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
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
Participants who have received previous CLL therapy, including investigational therapies
CLL requiring treatment according to IWCLL criteria
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.
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
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 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 pathological diagnosis of B-cell CLL
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
Patient has not received any prior treatment for CLL in the past
Patients must have a diagnosis of CLL/SLL and be previously treated
Presence of 2008 IWCLL/ NCI-WG indication for CLL treatment
Previous treatment for CLL- including therapy with immunomodulatory agents Revlimid or thalidomide, regardless of response
Must have a documented diagnosis of B-cell CLL.
Prior treatment for B-cell CLL.
confirmed CLL diagnosis and active CLL requiring treatment
not been treated for CLL before
prior CLL therapy
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
Patients with a diagnosis of CLL (or SLL) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL)
CLL that warrants treatment
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
No prior therapy for CLL other than corticosteroids for disease complications.
CLL that warrants treatment
Confirmed diagnosis of CLL or SLL based on IWCLL Criteria
No prior therapy for CLL other than corticosteroids for disease complications
CLL that warrants treatment
History of a non-CLL malignancy except for the following:
Manipulated B-CLL cells available (at least 6 injections)
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:
Intermediate or High risk, poor prognosis CLL/SLL
CLL and NHL Subjects:
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
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
For dose expansion monotherapy: CLL, HL, NHL
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 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.
For patients with SLL, CLL, or PLL, =< 20% of bone marrow cellularity involved by this process
At least one criterion for active disease as defined by the International Workshop on CLL.
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
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
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
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
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
PILOT III: CLL survivors
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
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).
Participant treats patients with CLL
Patient diagnosed with CLL < 60 days ago
Diagnosis of either Non-CLL B cell malignancy or CLL/SLL
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