NCT02966756
Recruiting
Phase 2
A Phase 2 Open-Label Study of the Efficacy of Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
InterventionsVenetoclax
DrugsVenetoclax
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- AbbVie
- Enrollment
- 110
- Locations
- 31
- Primary Endpoint
- Overall Response Rate (ORR)
Overview
Brief Summary
This is a Phase 2, open-label, multicenter study, evaluating the efficacy of venetoclax in participants with relapsed or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) either in presence of 17p deletion (Cohort 1) or those who have failed a B-receptor signaling pathway inhibitor (BCRI) therapy and who have also failed, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status (Cohort 2).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participant must have a diagnosis of relapsed or refractory chronic lymphocytic leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) that meets 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (iwCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines and the following:
- •Participant must have an indication for treatment according to the 2008 Modified iwCLL NCI-WG Guidelines.
- •SLL participant must have measurable disease (B-lymphocytosis greater than 5 × 10\^9/L or an enlarged lymph node(s) (Longest Diameter (LDi) \> 1.5 cm at baseline) or hepatomegaly or splenomegaly due to CLL).
- •SLL participant must have presence of lymphadenopathy and absence of cytopenias caused by a clonal marrow infiltrate.
- •Participant must have relapsed or refractory CLL/SLL after receiving at least one prior line of therapy.
- •Participants (in Cohort 1) must have 17p deletion, assessed by a central laboratory.
- •Participants (in Cohort 2) must meet both of the following:
- •Relapsed/refractory disease to B-Cell Receptor Signaling Pathway Inhibitor (BCRI) treatment;
- •And either of the following: (a) relapsed/refractory disease to chemoimmunotherapy (CIT), or (b) ineligible to receive CIT, defined as having known 17p deletion or TP53 mutation, or Cumulative Illness Rating Scale (CIRS) \>6 or calculated creatinine clearance \<70 mL/min, or participants in whom the investigator evaluated that the use of CIT was inappropriate.
- •Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to
Exclusion Criteria
- •Participant has undergone an allogeneic stem cell transplant.
- •Participant has developed Richter's transformation confirmed by biopsy.
- •Participant has prolymphocytic leukemia.
- •Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to screening), including autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP).
- •Participant has previously received venetoclax or other BCL-2 inhibitors.
- •Participant is known to be positive for Human Immunodeficiency Virus (HIV).
- •Participant has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.
- •Participant has received any of the following within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of venetoclax, or has not recovered to less than Common Toxicity Criteria for Adverse Events (CTCAE) grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
- •Any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy or targeted small molecule agents.
- •Investigational therapy, including targeted small molecule agents.
Arms & Interventions
Cohort 1: Venetoclax
Experimental
Participants with 17p deletion status will receive various doses of venetoclax once daily (QD).
Intervention: Venetoclax (Drug)
Cohort 2: Venetoclax
Experimental
Participants who have failed a B-Cell Receptor Signaling Pathway Inhibitor (BCRI) therapy and who have also failed, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status will receive various doses of venetoclax once daily (QD).
Intervention: Venetoclax (Drug)
Outcomes
Primary Outcomes
Overall Response Rate (ORR)
Time Frame: Measured up to 2 years after the last participant has enrolled in the study.
ORR is the proportion of participants with an overall response (complete remission \[CR\], plus complete remission with incomplete bone marrow recovery \[CRi\], plus nodular partial remission \[nPR\], plus partial remission \[PR\]) per the National Cancer Institute-Working Group (NCI-WG) guidelines as assessed by the Independent Review Committee (IRC).
Secondary Outcomes
- Time to 50% reduction in absolute lymphocyte count (ALC)(Measured up to 2 years after the last participant has enrolled into the study.)
- Complete Response Rate (CRR)(Measured up to 2 years after the last participant has enrolled into the study.)
- Duration of Overall Response (DOR)(Measured up to 2 years after the last participant has enrolled into the study.)
- Progression Free Survival (PFS)(Measured up to 5 years after the last participant has enrolled into the study.)
- Event Free Survival (EFS)(Measured up to 5 years after the last participant has enrolled into the study.)
- Time to Progression (TTP)(Measured up to 5 years after the last participant has enrolled into the study.)
- Overall Survival (OS)(Measured up to 5 years after the last participant has enrolled into the study.)
Investigators
Study Sites (31)
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