a study of me-401 in subjects with cll/sll, fl, and b-cell non hodgkin's lymphoma

Conditions: Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); Follicular Lymphoma (FL); Marginal Zone B Cell Lymphoma; Diffuse Large B-cell Lymphoma (DLBCL); High Grade Non-Hodgkin's Lymphoma; Mantle Cell Lymphoma (MCL)

Summary: a three-arm study of me-401 in subjects with relapsed/refractory cll/sll or fl, of me-401 in combination with rituximab in subjects with relapsed/refractory cll/sll or b-cell nhl, and of me-401 in combination with zanubrutinib in subjects with relapsed/refractory cll/sll or b-cell nhl

this is a three-arm study of me-401 alone, of me-401 in combination with rituximab, and of me-401 in combination with zanubrutinib in subjects with relapsed/refractory cll/sll or b cell nhl. the 3 arms of the study will be conducted in parallel, with subject allocation to me-401 alone, me-401 plus rituximab, or me-401 plus zanubrutinib based on disease type and availability of an open enrollment slot.

Eligibility criteria:
inclusion criteria mei-401 alone: * diagnosis of relapsed/refractory cll and/or relapsed/refractory sll or fl * no prior therapy with pi3kd inhibitors * no prior therapy with bruton tyrosine kinase (btk) inhibitors unless the subject was intolerant of btk therapy or subject had disease progression * subjects with cll/sll must have prior treatment with btk inhibitor and must have had progression or recurrence while on treatment of within 12 mos from btk treatment * subject must have failed at least 1 prior systemic therapy * qt-interval corrected according to fridericia's formula (qtcf) ≤ 450 milliseconds (ms) * left ventricular ejection fraction \> 50% * for subjects, except those with cll, must have at least one bi-dimensionally measurable nodal lesion \>1.5 cm, as defined by lugano classification * willingness to participate in collection of pharmacokinetic samples * a negative serum pregnancy test within 14 days of study day 0, for females of childbearing potential inclusion criteria me-401 in combination with rituximab * diagnosis of relapsed/refractory cll sll or fl, mzl, dlbcl and high-grade b-cell lymphoma. subjects must meet the following criteria for relapsed or refractory disease: * no prior therapy with pi3kδ inhibitors * no prior therapy with bruton tyrosine kinase (btk) inhibitors unless the subject was intolerant of btk therapy or subject had disease progression * subjects with cll, sll, fl, and mzl must have a failure of at least 1 prior systemic therapy and be considered by the investigator a candidate for therapy with a rituximab-based regimen; subjects with dlbcl and high-grade b-cell lymphoma must have a failure of at least 2 prior therapies. * qt-interval corrected according to fridericia's formula (qtcf) ≤450 milliseconds (ms) * left ventricular ejection fraction \> 50% * for subjects, except those with cll, must have at least one bi-dimensionally measurable nodal lesion \>1.5 cm, as defined by lugano classification * willingness to participate in collection of pharmacokinetic samples * a negative serum pregnancy test within 14 days of study day 0 for females of childbearing potential inclusion criteria me-401 in combination with zanubrutinib * diagnosis of relapsed/refractory cll or histologically-confirmed relapsed/refractory sll or fl, mzl, mcl, dlbcl nos (germinal center b-cell type or activated b-cell type) * no prior therapy with pi3kδ inhibitors * no prior therapy with btk inhibitors * subjects with cll, sll, fl, mcl, and mzl must have a failure of at least 1 prior systemic therapy, require treatment in the opinion of the investigator, and be considered by the investigator a candidate for therapy subjects with dlbcl and high-grade b-cell lymphoma must have a failure of at least 2 prior therapies * for subjects with sll, fl, mzl, mcl, dlbcl: at least one bi dimensionally measurable nodal lesion \> 1.5 cm in its longest diameter by ct scan or mri * qt-interval corrected according to fridericia's formula (qtcf) ≤ 450 milliseconds (msec) * left ventricular ejection fraction \> 50% as measured by echocardiogram or multigated acquisition (muga) scan * willingness to participate in collection of pharmacokinetic samples * for females of childbearing potential, a negative serum pregnancy test within 14 days of study day 0 exclusion criteria: * known histological transformation from cll to an aggressive lymphoma * uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia * subjects who have tested positive for hepatitis b surface antigen and/or hepatitis b core antibody * positive for hepatitis c virus antibody (hcv ab) or human immunodeficiency virus (hiv) antibody * ongoing drug-induced pneumonitis * history of clinically significant cardiovascular abnormalities * history of severe bleeding disorders (me-401 plus zanubrutinib arm only) * known central nervous system (cns) hemorrhage or stroke within 6 months prior to start of study drugs (me-401 plus zanubrutinib arm only)