Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Key Eligibility Criteria:
Provision of signed and dated written informed consent prior to any study specific procedures, sampling, or analyses.
Age 18 years or older.
Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise noted) of one of the following:
Note: For R/R cohorts, patients who have only received 1 line of therapy must be otherwise ineligible for, or intolerant to, available standard-of-care options.
NHL Cohorts:
a. MZL
i. R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after, or was refractory to, at least 1 prior therapy;
ii. Active disease requiring treatment.
b. FL i. R/R follicular lymphoma (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy ii. Active disease requiring treatment.
c. DLBCL
i. R/R DLBCL (including all subtypes of DLBCL) defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy and has either progressed following or is not a candidate for autologous stem cell transplant (due to comorbidities or non-responsiveness to salvage chemotherapy);
ii. Active disease requiring treatment.
d. Transformed indolent B-cell NHL
i. Any lymphoma otherwise eligible for Part 1 that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter’s transformation) are not eligible for Part 1;
ii. Active disease requiring treatment MCL Cohorts:
e. WHO-defined MCL
i. R/R MCL defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy;
ii. Requiring treatment in the opinion of the investigator.
CLL/SLL Cohorts:
f. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia criteria (Hallek et al 2008):
i. Meeting the following sets of prior treatment criteria:
(1) For R/R cohorts (Cohorts 1B, 1C, 2C, 2D, 2E, 3A, and 4A), disease that relapsed after, or was refractory to, at least 1 prior therapy.
For the venetoclax-treated cohort (Cohort 2E): prior therapy history must include progression after a therapy containing ≥ 2 months of venetoclax treatment (monotherapy or combination).
(2) For the treatment-naïve cohorts (Cohorts 3C and 4B), patients should have no prior treatment for CLL/SLL (other than 1 aborted regimen < 2 weeks in duration and > 4 weeks before enrollment).
Note: TN CLL/SLL patients will only be enrolled at investigational sites where this is allowed by regulatory authorities/local ethics.
ii. Requiring treatment WM Cohorts:
g. WHO-defined WM (clinical and definitive histologic diagnosis)
i. R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy
ii. Meeting at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenström’s Macroglobulinemia (Dimopoulos et al 2014)
4. Measurable disease by computed tomography/magnetic resonance imaging, defined as:
a. CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes on flow cytometry.
b. DLBCL, FL, MZL, MCL, or SLL: at least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in 2 perpendicular dimensions. For MZL isolated splenomegaly is considered measurable for this study. For MCL, clonal lymphocytes measured by flow cytometry is considered measurable.
c. WM: serum IgM level > 0.5 g/dL.
Key Exclusion Criteria:
Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer.
Underlying medical conditions that, in the investigator’s opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results.
Known central nervous system involvement by lymphoma/leukemia.
Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter’s syndrome.
Prior autologous stem cell transplant unless ≥ 3 months after transplant; or prior chimeric antigen receptor T-cell (CAR-T) therapy unless ≥ 3 months after cell infusion.
Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent.
History of a severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.
Eligibility last updated 9/12/22. Questions regarding updates should be directed to the study team contact.