Clinical Trials /

A Study of Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia in the Presence of 17p Deletion

NCT02966756

Description:

This is a Phase 2, open-label, single-arm, multicenter study, evaluating the efficacy of venetoclax in participants with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) in the presence of 17p deletion.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia in the Presence of 17p Deletion
  • Official Title: A Phase 2 Open-Label Study of the Efficacy of Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia in the Presence of 17p Deletion

Clinical Trial IDs

  • ORG STUDY ID: M14-728
  • SECONDARY ID: 2017-002413-54
  • NCT ID: NCT02966756

Conditions

  • Chronic Lymphocytic Leukemia (CLL)

Interventions

DrugSynonymsArms
VenetoclaxABT-199, GDC-0199Venetoclax

Purpose

This is a Phase 2, open-label, single-arm, multicenter study, evaluating the efficacy of venetoclax in participants with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) in the presence of 17p deletion.

Trial Arms

NameTypeDescriptionInterventions
VenetoclaxExperimentalVenetoclax will be administered orally starting with 20 mg once daily (QD); dose escalation will proceed weekly in the following progression: 50 mg QD, 100 mg QD, 200 mg QD, 400 mg QD, as tolerated.
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Participant must have a diagnosis of relapsed or refractory chronic lymphocytic
             leukemia (CLL) 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;

          -  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);

          -  Participant must have relapsed or refractory CLL after receiving at least one prior
             line of therapy

          -  Relapsed - must have completed at least 2 cycles of one prior line of therapy;

          -  Refractory - must have progressed after at least 1 cycle of one prior line of therapy;

          -  Participant must have 17p deletion, assessed by a central laboratory

          -  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

        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 (CTC) 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.

          -  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:Partial Remission (PR) rate
Time Frame:Measured up to 2 years after the last participant has enrolled into the study.
Safety Issue:
Description:PR rate is defined as the proportion of subjects who achieved nPR or PR per the NCI-WG criteria (determined by the IRC).
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:Percent 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:
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: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: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:Complete Remission (CR) rate
Time Frame:Measured up to 2 years after the last participant has enrolled into the study.
Safety Issue:
Description:CR rate is defined as the proportion of participants who achieved a CR or CRi per the NCI-WG criteria (determined by the IRC).

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

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