Description:
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 were
intolerant to or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status
(Cohort 2).
Title
- Brief Title: A Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- Official Title: A Phase 2 Open-Label Study of the Efficacy of Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
M14-728
- NCT ID:
NCT02966756
Conditions
- Chronic Lymphocytic Leukemia (CLL)
- Small Lymphocytic Lymphoma (SLL)
Interventions
| Drug | Synonyms | Arms |
|---|
| Venetoclax | ABT-199, GDC-0199, Venclexta | Cohort 1: Venetoclax |
Purpose
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 were
intolerant to or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status
(Cohort 2).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Cohort 1: Venetoclax | Experimental | Participants with 17p deletion status will receive various doses of venetoclax once daily (QD). | |
| Cohort 2: Venetoclax | Experimental | Participants who have failed a B-Cell Receptor Signaling Pathway Inhibitor (BCRI) therapy and who have also failed, were intolerant to, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status will receive various doses of venetoclax once daily (QD). | |
Eligibility Criteria
Inclusion Criteria:
- Participant must have a diagnosis of relapsed or refractory chronic lymphocytic
leukemia (CLL)/SLL that meets 2008 Modified International Workshop for Chronic
Lymphocytic Leukemia (iwCLL) NCI-WG Guidelines and the following:
- Participant must have an indication for treatment according to the 2008 Modified
iwCLL National Cancer Institute-Working Group (NCI-WG) Guidelines.
- CLL participant must have measurable disease (B-lymphocytosis greater than 5 ×
10^9/L or an enlarged lymph node(s) (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.
- Participant must have 17p deletion, assessed by a central laboratory.
- 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 17p
deletion, or Cumulative Illness Rating Scale (CIRS) >6 or calculated creatinine
clearance <70 mL/min.
- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score
of less than or equal to 2.
- Participant must have adequate bone marrow function, coagulation profile, renal, and
hepatic function, per laboratory reference range at Screening.
- No known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection.
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.
- 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 study drug, 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.
- Participant has known allergy to both xanthine oxidase inhibitors and rasburicase.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Overall Response Rate (ORR) |
| Time Frame: | Measured up to 2 years after the last participant has enrolled in the study. |
| Safety Issue: | |
| Description: | 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 Outcome Measures
| Measure: | Complete Response Rate (CRR) |
| Time Frame: | Measured up to 2 years after the last participant has enrolled into the study. |
| Safety Issue: | |
| Description: | CRR is defined as the proportion of subjects who achieved (CR + CRi) per the 2008 Modified iwCLL NCI-WG criteria. |
| Measure: | Duration of Overall Response (DOR) |
| Time Frame: | Measured up to 2 years after the last participant has enrolled into the study. |
| Safety Issue: | |
| Description: | DOR is defined as the number of days from the date of first (CR + CRi + nPR + PR) to the earliest disease progression or death |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | Measured up to 5 years after the last participant has enrolled into the study. |
| Safety Issue: | |
| Description: | PFS is defined as the number of days from the date of first dose to the date of earliest disease progression (determined by the IRC) or death. |
| Measure: | Event Free Survival (EFS) |
| Time Frame: | Measured up to 2 years after the last participant has enrolled into the study. |
| Safety Issue: | |
| Description: | EFS is defined as the number of days from the date of first dose to the date of earliest disease progression, death, or start of a new anti-leukemic therapy. |
| Measure: | Time to Progression (TTP) |
| Time Frame: | Measured up to 5 years after the last participant has enrolled into the study. |
| Safety Issue: | |
| Description: | TTP is defined as the number of days from the date of first dose to the date of earliest disease progression (determined by the IRC). |
| Measure: | Time to 50% reduction in absolute lymphocyte count (ALC) |
| Time Frame: | Measured up to 2 years after the last participant has enrolled into the study. |
| Safety Issue: | |
| Description: | Time to 50% reduction in ALC is defined as the number of days (hours if applicable) from the date of first dose to the date when the ALC has reduced to 50% of the baseline value |
| Measure: | Overall Survival (OS) |
| Time Frame: | Measured up to 5 years after the last participant has enrolled into the study. |
| Safety Issue: | |
| Description: | OS is defined as number of days from the date of first dose to the date of death. |
| Measure: | Percentage of participants who move on to stem cell transplant |
| Time Frame: | Measured up to 2 years after the last participant has enrolled into the study. |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | AbbVie |
Trial Keywords
- Relapsed chronic lymphocytic leukemia (CLL)
- Refractory chronic lymphocytic leukemia (CLL)
- 17p deletion
- venetoclax
- Leukemia
- Lymphoproliferative Disorders
- Small Lymphocytic Lymphoma (SLL)
- Venclexta
Last Updated
April 21, 2021
