Study Evaluating Venetoclax in Subjects With Hematological Malignancies

NCT02265731 | Completed Phase 1 DMC

• 1 other identifier: M13-834
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 14

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (7)

• Objective Response Rate (Phase 1)

  Approximately 48 months

• Minimal Residual Disease (MRD)

  Approximately 2 years

• Duration of Response

  Approximately 48 months

• Time to disease progression

  Approximately 48 months

• complete response or remission (CR) rate

  Approximately 48 months

Study Arms (4)

Arm A (Phase 1)

EXPERIMENTAL

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

Arm B (Phase 1)

EXPERIMENTAL

Step-up doses of venetoclax to the designated dose administered in participants with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)

Drug: venetoclax

Arm C (Phase 1)

EXPERIMENTAL

Step-up doses of venetoclax to the designated dose with the addition of azacitidine administered in participants with acute myeloid leukemia (AML)

Drug: azacitadine; Drug: venetoclax

Arm D (Phase 2)

EXPERIMENTAL

Step-up doses of venetoclax to the designated dose with the addition of rituximab in participants with R/R CLL

Drug: venetoclax; Drug: rituximab / IDEC-C2B8

Interventions

azacitadine DRUG

75 mg/m2 by IV infusion or subcutaneous dosing

Arm C (Phase 1)

venetoclax DRUG

Step-up doses of venetoclax to the designated cohort dose

Arm A (Phase 1); Arm B (Phase 1); Arm C (Phase 1); Arm D (Phase 2)

rituximab / IDEC-C2B8 DRUG

375 mg/m2 on Week 6

Arm D (Phase 2)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead
• Genentech, Inc.: collaborator

Study Sites (14)

NHO Nagoya Medical Center /ID# 129222

Nagoya, Aichi-ken, 460-0001, Japan

Location

Aichi Cancer Center Hospital /ID# 129061

Nagoya, Aichi-ken, 464-8681, Japan

Location

Nagoya City University Hospital /ID# 129278

Nagoya, Aichi-ken, 4678602, Japan

Location

University of Fukui Hospital /ID# 165801

Yoshida-gun, Fukui, 910-1193, Japan

Location

National Hospital Organization Kyushu Cancer Center /ID# 149741

Fukuoka, Fukuoka, 811-1395, Japan

Location

Kyushu University Hospital /ID# 163202

Fukuoka, Fukuoka, 812-8582, Japan

Location

Kobe City Medical Center General Hospital /ID# 170919

Kobe, Hyōgo, 650-0047, Japan

Location

Tohoku University Hospital /ID# 129275

Sendai, Miyagi, 9808574, Japan

Location

Kindai University Hospital /ID# 169554

Osakasayama-shi, Osaka, 589-8511, Japan

Location

Osaka University Hospital /ID# 169862

Suita-shi, Osaka, 565-0871, Japan

Location

National Cancer Center Hospital /ID# 129044

Chuo-ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital Of JFCR /ID# 129277

Koto-ku, Tokyo, 135-8550, Japan

Location

Toranomon Hospital /ID# 148229

Minato-ku, Tokyo, 105-8470, Japan

Location

NTT Medical Center Tokyo /ID# 166281

Shinagawa-ku, Tokyo, 141-8625, Japan

Location

Related Publications (1)

• 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.

  PMID: 33094474 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Lymphoproliferative Disorders; Lymphatic Diseases

Interventions

venetoclax; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2014
• First Posted: October 16, 2014
• Study Start: September 22, 2014
• Primary Completion: March 12, 2021
• Study Completion: March 12, 2021
• Last Updated: August 2, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

JP (14)