Study Evaluating Venetoclax in Subjects With Hematological Malignancies

Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02265731
• Other study ID #: M13-834
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 22, 2014
• Est. completion date: March 12, 2021

Study information

• Verified date: July 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: March 12, 2021
• Est. primary completion date: March 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Chronic Lymphocytic Leukemia (CLL)
• Hematologic Neoplasms
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Multiple Myeloma (MM)
• Neoplasms, Plasma Cell
• Non-Hodgkin Lymphoma (NHL)
• Small Lymphocytic Lymphoma (SLL)

Intervention

Drug:
• azacitadine
75 mg/m2 by IV infusion or subcutaneous dosing
• venetoclax
Step-up doses of venetoclax to the designated cohort dose
• rituximab / IDEC-C2B8
375 mg/m2 on Week 6
• rituximab / IDEC-C2B8
500 mg/m2 Week 10 Day 1 and thereafter

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital /ID# 129044	Chuo-ku	Tokyo
Japan	Kyushu University Hospital /ID# 163202	Fukuoka-shi	Fukuoka
Japan	National Hospital Organization Kyushu Cancer Center /ID# 149741	Fukuoka-shi	Fukuoka
Japan	Kobe City Medical Center General Hospital /ID# 170919	Kobe-shi	Hyogo
Japan	The Cancer Institute Hospital Of JFCR /ID# 129277	Koto-ku	Tokyo
Japan	Toranomon Hospital /ID# 148229	Minato-ku	Tokyo
Japan	Nagoya City University Hospital /ID# 129278	Nagoya shi	Aichi
Japan	Aichi Cancer Center Hospital /ID# 129061	Nagoya-shi	Aichi
Japan	NHO Nagoya Medical Center /ID# 129222	Nagoya-shi	Aichi
Japan	Kindai University Hospital /ID# 169554	Osakasayama-shi	Osaka
Japan	Tohoku University Hospital /ID# 129275	Sendai-shi	Miyagi
Japan	NTT Medical Center Tokyo /ID# 166281	Shinagawa-ku	Tokyo
Japan	Osaka University Hospital /ID# 169862	Suita-shi	Osaka
Japan	University of Fukui Hospital /ID# 165801	Yoshida-gun	Fukui

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Genentech, Inc.

Country where clinical trial is conducted

Japan, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants having treatment-emergent adverse events	Collect all adverse events at each visit	Approximately 2 years
Primary	Time to maximum plasma concentration (Tmax) of venetoclax		Approximately 8 days
Primary	Maximum plasma concentration (Cmax) of venetoclax		Approximately 8 days
Primary	Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax		Approximately 8 days
Primary	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	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
Secondary	Minimal Residual Disease (MRD)		Approximately 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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