Study Evaluating Venetoclax in Subjects With Hematological Malignancies

• ClinicalTrials.gov Identifier: NCT02265731
• Recruitment Status: Completed
• First Posted: October 16, 2014
• Last Update Posted: August 2, 2021
• Sponsor: AbbVie
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: October 15, 2014
• First Posted Date: October 16, 2014
• Last Update Posted Date: August 2, 2021
• Actual Study Start Date: September 22, 2014
• Actual Primary Completion Date: March 12, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 14, 2018)

• Number of participants having treatment-emergent adverse events [ Time Frame: Approximately 2 years ]
  Collect all adverse events at each visit
• Time to maximum plasma concentration (Tmax) of venetoclax [ Time Frame: Approximately 8 days ]
• Maximum plasma concentration (Cmax) of venetoclax [ Time Frame: Approximately 8 days ]
• Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax [ Time Frame: Approximately 8 days ]
• Objective Response Rate (Phase 2) [ Time Frame: Approximately 48 months ]
  The proportion of participants with response (e.g., partial, complete response) using IWCLL (International Workshop on Chronic Lymphocytic Leukemia) criteria for CLL participants will be computed for all participants with active disease at baseline (in the opinion of the investigator).

Original Primary Outcome Measures (submitted: October 15, 2014)

• Number of participants having treatment-emergent adverse events [ Time Frame: Approximately 2 years ]
  Collect all adverse events at each visit
• Maximum plasma concentration (Cmax) of ABT-199 [ Time Frame: Approximately 8 days ]
• Trough concentration (Ctrough) of ABT-199 [ Time Frame: Approximately 8 days ]
• Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of ABT-199 [ Time Frame: Approximately 8 days ]
• Time to maximum plasma concentration (Tmax) of ABT-199 [ Time Frame: Approximately 8 days ]

Current Secondary Outcome Measures (submitted: April 20, 2018)

• Objective Response Rate (Phase 1) [ Time Frame: Approximately 48 months ]
  The proportion of participants with response (e.g., partial, complete response) using IWG (International Working Group) response criteria for NHL participants, IMWG (International Myeloma Working Group) response criteria for multiple myeloma participants, IWCLL (International Workshop on Chronic Lymphocytic Leukemia) criteria for CLL participants or IWG (International Working Group) criteria for AML participants will be computed for all participants with active disease at baseline (in the opinion of the investigator).
• Minimal Residual Disease (MRD) [ Time Frame: Approximately 2 years ]
• Duration of Response [ Time Frame: Approximately 48 months ]
  Duration of response is defined as the number of days from the participant's initial response (e.g., partial, complete response per disease-appropriate response criteria) to the day that disease progression is objectively documented.
• Time to disease progression [ Time Frame: Approximately 48 months ]
  Time to disease progression is defined as the number of days from the date the subject started the study drug to the date of the subject's progression (all events of progression will be included).
• complete response or remission (CR) rate [ Time Frame: Approximately 48 months ]
  CR rate will be defined as the proportion of participants who achieved a complete response or remission (CR) or complete response with incomplete bone marrow recovery or complete remission with incomplete count recovery (CRi) per the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria.
• Partial response or remission (PR) rate [ Time Frame: Approximately 48 months ]
  PR rate will be defined as the proportion of subjects who achieved a nodular PR (nPR) or PR per the 2008 IWCLL criteria.
• Progression Free Survival (PFS) [ Time Frame: Approximately 48 months ]
  Duration of progression-free survival (PFS) will be defined as the number of days from the date of first dose to the date of earliest disease progression or death.

Original Secondary Outcome Measures (submitted: October 15, 2014)

• Objective Response Rate [ Time Frame: Approximately 48 months ]
  The proportion of participants with response (e.g., partial, complete response) using IWG (International Working Group) response criteria for NHL participants or IMWG (International Myeloma Working Group) response criteria for multiple myeloma participants will be computed for all participants with active disease at baseline (in the opinion of the investigator).
• Duration of Response [ Time Frame: Approximately 48 months ]
  Duration of response is defined as the number of days from the participant's initial response (e.g., partial, complete response per disease-appropriate response criteria) to the day that disease progression is objectively documented.
• Minimal Residual Disease (MRD) [ Time Frame: Approximately 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating Venetoclax in Subjects With Hematological Malignancies
• Official Title: A Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of Venetoclax in Japanese Subjects With Hematological Malignancies
• Brief Summary: This study is evaluating the safety, pharmacokinetic profile and efficacy of venetoclax under a once daily dosing schedule in Japanese participants with hematological malignancies.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Hodgkin Lymphoma (NHL)
• Multiple Myeloma (MM)
• Chronic Lymphocytic Leukemia (CLL)
• Small Lymphocytic Lymphoma (SLL)
• Acute Myeloid Leukemia (AML)

Intervention

• Drug: azacitadine
  75 mg/m2 by IV infusion or subcutaneous dosing
• Drug: venetoclax
  Step-up doses of venetoclax to the designated cohort dose
• Drug: rituximab / IDEC-C2B8
  375 mg/m2 on Week 6
• Drug: rituximab / IDEC-C2B8
  500 mg/m2 Week 10 Day 1 and thereafter

Study Arms

• Experimental: Arm A (Phase 1)
  Step-up doses of venetoclax to the designated cohort dose administered in participants with relapsed or refractory (R/R) Non-Hodgkin lymphoma (NHL) or multiple myeloma (MM)
  Intervention: Drug: venetoclax
• Experimental: Arm B (Phase 1)
  Step-up doses of venetoclax to the designated dose administered in participants with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
  Intervention: Drug: venetoclax
• Experimental: Arm C (Phase 1)
  Step-up doses of venetoclax to the designated dose with the addition of azacitidine administered in participants with acute myeloid leukemia (AML)
  Interventions:

  • Drug: azacitadine
  • Drug: venetoclax
• Experimental: Arm D (Phase 2)
  Step-up doses of venetoclax to the designated dose with the addition of rituximab in participants with R/R CLL
  Interventions:

  • Drug: venetoclax
  • Drug: rituximab / IDEC-C2B8
  • Drug: rituximab / IDEC-C2B8

• Publications *: Izutsu K, Yamamoto K, Kato K, Ishikawa T, Fukuhara N, Terui Y, Choi I, Humphrey K, Kim SY, Okubo S, Ogawa N, Nishimura Y, Salem AH, Maruyama D. Phase 1/2 study of venetoclax, a BCL-2 inhibitor, in Japanese patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. Int J Hematol. 2021 Mar;113(3):370-380. doi: 10.1007/s12185-020-03024-3. Epub 2020 Oct 23.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 29, 2018): 38
• Original Estimated Enrollment (submitted: October 15, 2014): 24
• Actual Study Completion Date: March 12, 2021
• Actual Primary Completion Date: March 12, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants must have histologically documented diagnosis of NHL (and exhausted options considered standard of care) as defined in the World Health Organization classification scheme and relapsed following or be refractory to standard treatments such as R-CHOP, R-CVP, or fludarabine based regimens. Participants with other lymphoproliferative diseases can be considered in consultation with the AbbVie medical monitor
• Relapsed or refractory multiple myeloma participants must have been previously treated with at least one prior line of therapy and have measurable disease
• Chronic lymphocytic leukemia/small lymphocytic lymphoma participants must have relapsed or be refractory to standard treatments such as fludarabine based regimens or alkylator based regimens
• Untreated AML subjects or Relapsed or refractory AML subjects must have been previously treated with at least one prior line of therapy
• Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1; adequate bone marrow independent of growth factor support per local laboratory reference range; and adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening
• Participants with a history of autologous or allogenic stem cell transplantation must have adequate blood counts independent of growth factor support and have recovered from any transplant-related toxicity(s) and be at least 100 days post-autologous transplant (multiple myeloma) or 6 month post-autologous transplant (NHL) prior to first dose of study drug or at least 6 months post-allogenic transplant (multiple myeloma) prior to first dose of study drug and not have active graft-versus-host disease (GVHD), i.e., requiring treatment

Exclusion Criteria:

• NHL participants who have undergone an allogeneic stem cell transplant or were diagnosed with Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia
• Participant tested positive for HIV
• Participant has a cardiovascular disability status of New York Heart Association Class greater or equal to 2
• Participant has a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the Investigator would adversely affect his/her participating in this study.
• Participant received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT02265731
• Other Study ID Numbers: M13-834
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• 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

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Genentech, Inc.

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: July 2021