Study Evaluating Venetoclax in Subjects With Hematological Malignancies

A Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of Venetoclax in Japanese Subjects With Hematological Malignancies

This study is evaluating the safety, pharmacokinetic profile and efficacy of venetoclax under a once daily dosing schedule in Japanese participants with hematological malignancies.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); Acute Myeloid Leukemia (AML); Multiple Myeloma (MM); Non-Hodgkin Lymphoma (NHL)
• Intervention / Treatment: Drug: venetoclax; Drug: azacitadine; Drug: rituximab / IDEC-C2B8; Drug: rituximab / IDEC-C2B8

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya shi, Aichi, Japan, 4678602
      • Nagoya City University Hospital /ID# 129278
    • Nagoya-shi, Aichi, Japan, 460-0001
      • NHO Nagoya Medical Center /ID# 129222
    • Nagoya-shi, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital /ID# 129061
  • Fukui
    • Yoshida-gun, Fukui, Japan, 910-1193
      • University of Fukui Hospital /ID# 165801
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center /ID# 149741
    • Fukuoka-shi, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital /ID# 163202
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital /ID# 170919
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 9808574
      • Tohoku University Hospital /ID# 129275
  • Osaka
    • Osakasayama-shi, Osaka, Japan, 589-8511
      • Kindai University Hospital /ID# 169554
    • Suita-shi, Osaka, Japan, 565-0871
      • Osaka University Hospital /ID# 169862
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 129044
    • Koto-ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital Of JFCR /ID# 129277
    • Minato-ku, Tokyo, Japan, 105-8470
      • Toranomon Hospital /ID# 148229
    • Shinagawa-ku, Tokyo, Japan, 141-8625
      • NTT Medical Center Tokyo /ID# 166281

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)	Drug: venetoclax; Step-up doses of venetoclax to the designated cohort dose
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)	Drug: venetoclax; Step-up doses of venetoclax to the designated cohort dose
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)	Drug: venetoclax; Step-up doses of venetoclax to the designated cohort dose; Drug: azacitadine; 75 mg/m2 by IV infusion or subcutaneous dosing
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	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants having treatment-emergent adverse events	Collect all adverse events at each visit	Approximately 2 years
Time to maximum plasma concentration (Tmax) of venetoclax		Approximately 8 days
Maximum plasma concentration (Cmax) of venetoclax		Approximately 8 days
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax		Approximately 8 days
Objective Response Rate (Phase 2)	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).	Approximately 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (Phase 1)	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).	Approximately 48 months
Minimal Residual Disease (MRD)		Approximately 2 years
Duration of Response	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.	Approximately 48 months
Time to disease progression	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).	Approximately 48 months
complete response or remission (CR) rate	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.	Approximately 48 months
Partial response or remission (PR) rate	PR rate will be defined as the proportion of subjects who achieved a nodular PR (nPR) or PR per the 2008 IWCLL criteria.	Approximately 48 months
Progression Free Survival (PFS)	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.	Approximately 48 months

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Genentech, Inc.

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2014
• Primary Completion (Actual): March 12, 2021
• Study Completion (Actual): March 12, 2021

Study Registration Dates

• First Submitted: October 15, 2014
• First Submitted That Met QC Criteria: October 15, 2014
• First Posted (Estimate): October 16, 2014

Study Record Updates

• Last Update Posted (Actual): August 2, 2021
• Last Update Submitted That Met QC Criteria: July 29, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Lymphoma, Non-Hodgkin; acute myeloid leukemia; refractory chronic lymphocytic leukemia; refractory multiple myeloma; Lymphoproliferative Disorders; Lymphatic Diseases; relapsed multiple myeloma; small lymphocytic lymphoma; relapsed chronic lymphocytic leukemia; relapsed small lymphocytic lymphoma; refractory small lymphocytic lymphoma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Leukemia, B-Cell; Lymphoma; Hematologic Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Venetoclax; Rituximab
• Other Study ID Numbers: M13-834

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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