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Study Evaluating Venetoclax in Subjects With Hematological Malignancies

Primary Purpose

Non-Hodgkin Lymphoma (NHL), Multiple Myeloma (MM), Chronic Lymphocytic Leukemia (CLL)

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

azacitadine

venetoclax

rituximab / IDEC-C2B8

About this trial

This is an interventional treatment trial for Non-Hodgkin Lymphoma (NHL) focused on measuring 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

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Nagoya City University Hospital /ID# 129278
NHO Nagoya Medical Center /ID# 129222
Aichi Cancer Center Hospital /ID# 129061
University of Fukui Hospital /ID# 165801
National Hospital Organization Kyushu Cancer Center /ID# 149741
Kyushu University Hospital /ID# 163202
Kobe City Medical Center General Hospital /ID# 170919
Tohoku University Hospital /ID# 129275
Kindai University Hospital /ID# 169554
Osaka University Hospital /ID# 169862
National Cancer Center Hospital /ID# 129044
The Cancer Institute Hospital Of JFCR /ID# 129277
Toranomon Hospital /ID# 148229
NTT Medical Center Tokyo /ID# 166281

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Arm A (Phase 1)

Arm B (Phase 1)

Arm C (Phase 1)

Arm D (Phase 2)

Arm Description

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)

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

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

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

Outcomes

Primary Outcome Measures

Number of participants having treatment-emergent adverse events

Collect all adverse events at each visit

Time to maximum plasma concentration (Tmax) of venetoclax

Maximum plasma concentration (Cmax) of venetoclax

Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax

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).

Secondary Outcome Measures

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).

Minimal Residual Disease (MRD)

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.

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).

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.

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.

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.

Full Information

NCT ID

NCT02265731

First Posted

October 15, 2014

Last Updated

July 29, 2021

Sponsor

AbbVie

Collaborators

Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02265731

Brief Title

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

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

September 22, 2014 (Actual)

Primary Completion Date

March 12, 2021 (Actual)

Study Completion Date

March 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AbbVie

Collaborators

Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A (Phase 1)

Arm Type

Experimental

Arm Description

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)

Arm Title

Arm B (Phase 1)

Arm Type

Experimental

Arm Description

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

Arm Title

Arm C (Phase 1)

Arm Type

Experimental

Arm Description

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

Arm Title

Arm D (Phase 2)

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

azacitadine

Intervention Description

75 mg/m2 by IV infusion or subcutaneous dosing

Intervention Type

Drug

Intervention Name(s)

venetoclax

Intervention Description

Step-up doses of venetoclax to the designated cohort dose

Intervention Type

Drug

Intervention Name(s)

rituximab / IDEC-C2B8

Intervention Description

375 mg/m2 on Week 6

Intervention Type

Drug

Intervention Name(s)

rituximab / IDEC-C2B8

Intervention Description

500 mg/m2 Week 10 Day 1 and thereafter

Primary Outcome Measure Information:

Title

Number of participants having treatment-emergent adverse events

Description

Collect all adverse events at each visit

Time Frame

Approximately 2 years

Title

Time to maximum plasma concentration (Tmax) of venetoclax

Time Frame

Approximately 8 days

Title

Maximum plasma concentration (Cmax) of venetoclax

Time Frame

Approximately 8 days

Title

Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax

Time Frame

Approximately 8 days

Title

Objective Response Rate (Phase 2)

Description

Time Frame

Approximately 48 months

Secondary Outcome Measure Information:

Title

Objective Response Rate (Phase 1)

Description

Time Frame

Approximately 48 months

Title

Minimal Residual Disease (MRD)

Time Frame

Approximately 2 years

Title

Duration of Response

Description

Time Frame

Approximately 48 months

Title

Time to disease progression

Description

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).

Time Frame

Approximately 48 months

Title

complete response or remission (CR) rate

Description

Time Frame

Approximately 48 months

Title

Partial response or remission (PR) rate

Description

PR rate will be defined as the proportion of subjects who achieved a nodular PR (nPR) or PR per the 2008 IWCLL criteria.

Time Frame

Approximately 48 months

Title

Progression Free Survival (PFS)

Description

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.

Time Frame

Approximately 48 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

AbbVie Inc.

Organizational Affiliation

AbbVie

Official's Role

Study Director

Facility Information:

Facility Name

Nagoya City University Hospital /ID# 129278

City

Nagoya shi

State/Province

Aichi

ZIP/Postal Code

4678602

Country

Japan

Facility Name

NHO Nagoya Medical Center /ID# 129222

City

Nagoya-shi

State/Province

Aichi

ZIP/Postal Code

460-0001

Country

Japan

Facility Name

Aichi Cancer Center Hospital /ID# 129061

City

Nagoya-shi

State/Province

Aichi

ZIP/Postal Code

464-8681

Country

Japan

Facility Name

University of Fukui Hospital /ID# 165801

City

Yoshida-gun

State/Province

Fukui

ZIP/Postal Code

910-1193

Country

Japan

Facility Name

National Hospital Organization Kyushu Cancer Center /ID# 149741

City

Fukuoka-shi

State/Province

Fukuoka

ZIP/Postal Code

811-1395

Country

Japan

Facility Name

Kyushu University Hospital /ID# 163202

City

Fukuoka-shi

State/Province

Fukuoka

ZIP/Postal Code

812-8582

Country

Japan

Facility Name

Kobe City Medical Center General Hospital /ID# 170919

City

Kobe-shi

State/Province

Hyogo

ZIP/Postal Code

650-0047

Country

Japan

Facility Name

Tohoku University Hospital /ID# 129275

City

Sendai-shi

State/Province

Miyagi

ZIP/Postal Code

9808574

Country

Japan

Facility Name

Kindai University Hospital /ID# 169554

City

Osakasayama-shi

State/Province

Osaka

ZIP/Postal Code

589-8511

Country

Japan

Facility Name

Osaka University Hospital /ID# 169862

City

Suita-shi

State/Province

Osaka

ZIP/Postal Code

565-0871

Country

Japan

Facility Name

National Cancer Center Hospital /ID# 129044

City

Chuo-ku

State/Province

Tokyo

ZIP/Postal Code

104-0045

Country

Japan

Facility Name

The Cancer Institute Hospital Of JFCR /ID# 129277

City

Koto-ku

State/Province

Tokyo

ZIP/Postal Code

135-8550

Country

Japan

Facility Name

Toranomon Hospital /ID# 148229

City

Minato-ku

State/Province

Tokyo

ZIP/Postal Code

105-8470

Country

Japan

Facility Name

NTT Medical Center Tokyo /ID# 166281

City

Shinagawa-ku

State/Province

Tokyo

ZIP/Postal Code

141-8625

Country

Japan

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing Time Frame

Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.

IPD Sharing 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.

IPD Sharing URL

https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

Citations:

PubMed Identifier

33094474

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.

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Study Evaluating Venetoclax in Subjects With Hematological Malignancies

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