Study Evaluating Venetoclax in Subjects With Hematological Malignancies

Sponsor

AbbVie (Industry)

Overall Status

Completed

CT.gov ID

NCT02265731

Collaborator

Genentech, Inc. (Industry)

Enrollment

Locations

Arms

77.6

Actual Duration (Months)

2.7

Patients Per Site

Patients Per Site Per Month

Study Details

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 Drug: rituximab / IDEC-C2B8	Phase 1/Phase 2

Study Design

Study Type:

Interventional

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 :

Sep 22, 2014

Actual Primary Completion Date :

Mar 12, 2021

Actual Study Completion Date :

Mar 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

Number of participants having treatment-emergent adverse events [Approximately 2 years]
Collect all adverse events at each visit
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) [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

Objective Response Rate (Phase 1) [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) [Approximately 2 years]
Duration of Response [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 [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 [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 [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) [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

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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