a study of duvelisib and venetoclax in subjects with relapsed or refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, or indolent or aggressive non-hodgkin lymphoma, who have not previously received a bcl-2 or pi3k inhibitor

Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Non-Hodgkin Lymphoma

Summary: this study is designed to assess the safety, pharmacokinetics, drug-drug interactions, and determine the recommended phase 2 doses of co administered duvelisib and venetoclax in participants with relapsed or refractory chronic lymphocytic leukemia (cll), small lymphocytic lymphoma, or indolent or aggressive non-hodgkin lymphoma, who have not previously received a bcl-2 or phosphoinositide 3-kinase (pi3k) inhibitor. the phase 2 portion of the study will preliminarily evaluate efficacy, and expand the toxicity evaluation.


Eligibility criteria:
inclusion criteria: - subject must have either • relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (for waves 2 or 3) * subject has evaluable disease and requires treatment in the opinion of the investigator. * subject must have relapsed following or be refractory to ≥ 1 standard treatments such as fludarabine based regimens (f, fc, fr, fcr), alkylator (chlorambucil, bendamustine) based regimens, or bruton's tyrosine kinase inhibitor (ibrutinib). or • relapsed or refractory indolent non-hodgkin lymphoma or aggressive non-hodgkin lymphoma (for waves 1, 2, or 3, unless otherwise indicated) * subject must have histologically documented diagnosis of a follicular lymphoma or marginal zone lymphoma. * subject must have histologically documented diagnosis of a diffuse large b-cell lymphoma (excluding richter's transformation), non-cutaneous t-cell lymphoma, or mantle cell lymphoma (mcl) (mcl wave 3 only) * subject has evaluable disease and requires treatment in the opinion of the investigator. * subject must have relapsed following or be refractory to ≥ 1 standard treatments such as r-chop, r-cvp, bendamustine, lenalidomide-rituximab, or fludarabine-based regimens. * subject has an eastern cooperative oncology group (ecog) performance score of less than or equal to 2. * subject must have adequate bone marrow independent of growth factor support per local laboratory reference range at screening. * subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at screening. * nhl subjects who have a history of an autologous stem cell transplant (e.g., bone marrow) must be \> 6 months post-transplant (prior to the first dose of study drug) and must not require any growth factor support. exclusion criteria: * subject has been previously treated with a bcl-2 or pi3k inhibitor. * subject is a candidate to receive another second-line therapy approved for usage by the local health authority. * subject is appropriate for a stem cell transplant or has undergone an allogeneic stem cell transplant. * subject has received any of the following within 14 days or 5 drug half-lives (whichever is shortest) prior to the first dose of duvelisib or venetoclax, or has not recovered to less than grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy: * any anti-cancer therapy including chemotherapy or radiotherapy; * investigational therapy, including targeted small molecule agents. * subject has received biologic agents (e.g., monoclonal antibodies) for anti-neoplastic treatment within 30 days prior to first dose of duvelisib or venetoclax. * subject has received live or live attenuated vaccines within 6 weeks prior to first dose of duvelisib or venetoclax. * subject has received the following within 7 days prior to the first dose of duvelisib or venetoclax: * steroid therapy for anti-neoplastic treatment; * strong and moderate cyp3a inhibitors; * strong and moderate cyp3a inducers; * chronic immunosuppressants, other than corticosteroids given at daily dose \< 20 mg prednisone equivalent for itp or aiha.

Keywords: refractory lymphoma relapsed leukemia