Non-Hodgkin Lymphoma (NHL)Phase 1/2NCT02265731
Study Evaluating Venetoclax in Subjects With Hematological Malignancies
A Phase 1/2 study testing azacitadine, venetoclax and rituximab / IDEC-C2B8 in people with Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM), run by AbbVie at 14 sites in Japan.
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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma (NHL), Multiple Myeloma (MM), Chronic Lymphocytic Leukemia (CLL)
- What is being tested?
- azacitadine, venetoclax and rituximab / IDEC-C2B8
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 14 sitesJapan
- Study dates
- 22 Sep 2014to 12 Mar 2021
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Japan14 sites
National Cancer Center Hospital /ID# 129044
Chuo-ku, Tokyo, 104-0045
National Hospital Organization Kyushu Cancer Center /ID# 149741
Fukuoka, Fukuoka, 811-1395
Kyushu University Hospital /ID# 163202
Fukuoka, Fukuoka, 812-8582
Kobe City Medical Center General Hospital /ID# 170919
Kobe, Hyōgo, 650-0047
The Cancer Institute Hospital Of JFCR /ID# 129277
Koto-ku, Tokyo, 135-8550
Toranomon Hospital /ID# 148229
Minato-ku, Tokyo, 105-8470
NHO Nagoya Medical Center /ID# 129222
Nagoya, Aichi-ken, 460-0001
Aichi Cancer Center Hospital /ID# 129061
Nagoya, Aichi-ken, 464-8681
Nagoya City University Hospital /ID# 129278
Nagoya, Aichi-ken, 4678602
Kindai University Hospital /ID# 169554
Osakasayama-shi, Osaka, 589-8511
Tohoku University Hospital /ID# 129275
Sendai, Miyagi, 9808574
NTT Medical Center Tokyo /ID# 166281
Shinagawa-ku, Tokyo, 141-8625
Osaka University Hospital /ID# 169862
Suita-shi, Osaka, 565-0871
University of Fukui Hospital /ID# 165801
Yoshida-gun, Fukui, 910-1193
About this study
Official title: A Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of Venetoclax in Japanese Subjects With Hematological Malignancies
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)
- Being tested
- azacitadine, venetoclax, rituximab / IDEC-C2B8
- 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
- Medical subject headings
- Lymphoma, Non-Hodgkin, Multiple Myeloma, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myeloid, Acute, Lymphoproliferative Disorders, Lymphatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
azacitadineDrug
75 mg/m2 by IV infusion or subcutaneous dosing
venetoclaxDrug
Step-up doses of venetoclax to the designated cohort dose
rituximab / IDEC-C2B8Drug
375 mg/m2 on Week 6
rituximab / IDEC-C2B8Drug
500 mg/m2 Week 10 Day 1 and thereafter
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: 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) Receives: 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 Receives: Drug: venetoclax; Drug: rituximab / IDEC-C2B8 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants having treatment-emergent adverse events
Collect all adverse events at each visit
Measured: Approximately 2 years
Time to maximum plasma concentration (Tmax) of venetoclax
Measured: Approximately 8 days
Maximum plasma concentration (Cmax) of venetoclax
Measured: Approximately 8 days
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax
Measured: 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).
Measured: Approximately 48 months
Secondary outcomes (7)
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).
Measured: Approximately 48 months
Minimal Residual Disease (MRD)
Measured: Approximately 2 years
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.
Measured: Approximately 48 months
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).
Measured: Approximately 48 months
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.
Measured: Approximately 48 months
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.
Measured: Approximately 48 months
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.
Measured: Approximately 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2014 (estimated)
- Study start22 Sep 2014
- Primary completion12 Mar 2021
- Study completion12 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Hodgkin Lymphoma (NHL)Studies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- AbbVie Inc., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02265731
- Sponsor's protocol ID
- M13-834
- Status last verified
- Jul 2021
- First submitted
- 15 Oct 2014
- Last updated
- 2 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 33094474