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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-Hodgkin Lymphoma (NHL); Multiple Myeloma (MM); Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); Acute Myeloid Leukemia (AML)	Drug: azacitadine; Drug: venetoclax; Drug: rituximab / IDEC-C2B8	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of Venetoclax in Japanese Subjects With Hematological Malignancies
• Actual Study Start Date: September 22, 2014
• Actual Primary Completion Date: March 12, 2021
• Actual Study Completion Date: March 12, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of participants having treatment-emergent adverse events [ Time Frame: Approximately 2 years ]
   Collect all adverse events at each visit
2. Time to maximum plasma concentration (Tmax) of venetoclax [ Time Frame: Approximately 8 days ]
3. Maximum plasma concentration (Cmax) of venetoclax [ Time Frame: Approximately 8 days ]
4. Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax [ Time Frame: Approximately 8 days ]
5. 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).

Secondary Outcome Measures :

1. 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).
2. Minimal Residual Disease (MRD) [ Time Frame: Approximately 2 years ]
3. 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.
4. 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).
5. 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.
6. 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.
7. 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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

Japan

Nagoya City University Hospital /ID# 129278

Nagoya shi, Aichi, Japan, 4678602

NHO Nagoya Medical Center /ID# 129222

Nagoya-shi, Aichi, Japan, 460-0001

Aichi Cancer Center Hospital /ID# 129061

Nagoya-shi, Aichi, Japan, 464-8681

University of Fukui Hospital /ID# 165801

Yoshida-gun, Fukui, Japan, 910-1193

National Hospital Organization Kyushu Cancer Center /ID# 149741

Fukuoka-shi, Fukuoka, Japan, 811-1395

Kyushu University Hospital /ID# 163202

Fukuoka-shi, Fukuoka, Japan, 812-8582

Kobe City Medical Center General Hospital /ID# 170919

Kobe-shi, Hyogo, Japan, 650-0047

Tohoku University Hospital /ID# 129275

Sendai-shi, Miyagi, Japan, 9808574

Kindai University Hospital /ID# 169554

Osakasayama-shi, Osaka, Japan, 589-8511

Osaka University Hospital /ID# 169862

Suita-shi, Osaka, Japan, 565-0871

National Cancer Center Hospital /ID# 129044

Chuo-ku, Tokyo, Japan, 104-0045

The Cancer Institute Hospital Of JFCR /ID# 129277

Koto-ku, Tokyo, Japan, 135-8550

Toranomon Hospital /ID# 148229

Minato-ku, Tokyo, Japan, 105-8470

NTT Medical Center Tokyo /ID# 166281

Shinagawa-ku, Tokyo, Japan, 141-8625

Sponsors and Collaborators

AbbVie

Genentech, Inc.

Investigators

• Study Director: AbbVie Inc.; AbbVie

More Information

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.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02265731
• Other Study ID Numbers: M13-834
• First Posted: October 16, 2014
• Last Update Posted: August 2, 2021
• Last Verified: July 2021

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)
• 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 multiple myeloma; refractory multiple myeloma; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Lymphatic Diseases; relapsed chronic lymphocytic leukemia; small lymphocytic lymphoma; relapsed small lymphocytic lymphoma; refractory small lymphocytic lymphoma; refractory chronic lymphocytic leukemia; acute myeloid leukemia

Additional relevant MeSH terms:

Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Hematologic Neoplasms; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Neoplasms by Site; Rituximab; Venetoclax