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

• ClinicalTrials.gov Identifier: NCT02966756
• Recruitment Status: Recruiting
• First Posted: November 17, 2016
• Last Update Posted: November 14, 2019
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Chronic Lymphocytic Leukemia (CLL)	Drug: Venetoclax	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 12, 2017
• Estimated Primary Completion Date: August 29, 2021
• Estimated Study Completion Date: April 29, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Venetoclax; Venetoclax 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.	Drug: Venetoclax; tablet; Other Names: ABT-199; GDC-0199

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. Partial Remission (PR) rate [ Time Frame: Measured up to 2 years after the last participant has enrolled into the study. ]
   PR rate is defined as the proportion of subjects who achieved nPR or PR per the NCI-WG criteria (determined by the IRC).
2. Event Free Survival (EFS) [ Time Frame: Measured up to 2 years after the last participant has enrolled into the study. ]
   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.
3. 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. ]
4. Overall Survival (OS) [ Time Frame: Measured up to 5 years after the last participant has enrolled into the study. ]
   OS is defined as number of days from the date of first dose to the date of death.
5. Progression Free Survival (PFS) [ Time Frame: Measured up to 5 years after the last participant has enrolled into the study. ]
   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.
6. Time to Progression (TTP) [ Time Frame: Measured up to 5 years after the last participant has enrolled into the study. ]
   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).
7. 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. ]
   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
8. Complete Remission (CR) rate [ Time Frame: Measured up to 2 years after the last participant has enrolled into the study. ]
   CR rate is defined as the proportion of participants who achieved a CR or CRi per the NCI-WG criteria (determined by the IRC).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: ABBVIE CALL CENTER; 847.283.8955; abbvieclinicaltrials@abbvie.com

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Sponsors and Collaborators

AbbVie

Investigators

• Study Director: AbbVie Inc.; AbbVie

More Information

Additional Information:

Related Info 

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02966756 History of Changes
• Other Study ID Numbers: M14-728; 2017-002413-54 ( EudraCT Number )
• First Posted: November 17, 2016
• Last Update Posted: November 14, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by AbbVie:

Relapsed chronic lymphocytic leukemia (CLL); Refractory chronic lymphocytic leukemia (CLL); 17p deletion; venetoclax; Leukemia; Lymphoproliferative Disorders

Additional relevant MeSH terms:

Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Venetoclax; Antineoplastic Agents