Clinical trial NCT02265731: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2014-10-16
Enrollment: 38
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of participants having treatment-emergent adverse events
timeFrame: Approximately 2 years
measure: Time to maximum plasma concentration (Tmax) of venetoclax
timeFrame: Approximately 8 days
measure: Maximum plasma concentration (Cmax) of venetoclax
timeFrame: Approximately 8 days
measure: Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax
timeFrame: Approximately 8 days
measure: Objective Response Rate (Phase 2)
timeFrame: Approximately 48 months
Secondary outcomes:
measure: Objective Response Rate (Phase 1)
timeFrame: Approximately 48 months
measure: Minimal Residual Disease (MRD)
timeFrame: Approximately 2 years
measure: Duration of Response
timeFrame: Approximately 48 months
measure: Time to disease progression
timeFrame: Approximately 48 months
measure: complete response or remission (CR) rate
timeFrame: Approximately 48 months
measure: Partial response or remission (PR) rate
timeFrame: Approximately 48 months
measure: Progression Free Survival (PFS)
timeFrame: Approximately 48 months
Other outcomes:
Locations:
city: Nagoya shi
country: Japan
facility: Nagoya City University Hospital /ID# 129278
state: Aichi
city: Nagoya-shi
country: Japan
facility: NHO Nagoya Medical Center /ID# 129222
state: Aichi
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital /ID# 129061
state: Aichi
city: Yoshida-gun
country: Japan
facility: University of Fukui Hospital /ID# 165801
state: Fukui
city: Fukuoka-shi
country: Japan
facility: National Hospital Organization Kyushu Cancer Center /ID# 149741
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital /ID# 163202
state: Fukuoka
city: Kobe-shi
country: Japan
facility: Kobe City Medical Center General Hospital /ID# 170919
state: Hyogo
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital /ID# 129275
state: Miyagi
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital /ID# 169554
state: Osaka
city: Suita-shi
country: Japan
facility: Osaka University Hospital /ID# 169862
state: Osaka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 129044
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital Of JFCR /ID# 129277
state: Tokyo
city: Minato-ku
country: Japan
facility: Toranomon Hospital /ID# 148229
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: NTT Medical Center Tokyo /ID# 166281
state: Tokyo
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.