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

AbbVie

Status and phase

Withdrawn

Phase 1

Conditions

Small Lymphocytic Lymphoma

Chronic Lymphocytic Leukemia

Non-Hodgkin Lymphoma

Treatments

Drug: Duvelisib

Drug: Venetoclax

Study type

Interventional

Funder types

Industry

Identifiers

NCT02640833

2015-003302-16 (EudraCT Number)

M15-330

Details and patient eligibility

About

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.

Sex

All

Ages

18 to 99 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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).

• 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.