- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03422393
Venetoclax With High-dose Ibrutinib for CLL Progressing on Single Agent Ibrutinib
A Phase 1 Clinical Trial to Evaluate Venetoclax With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.
Study Overview
Status
Intervention / Treatment
Detailed Description
This is phase 1 study for patients with CLL or small lymphocytic lymphoma (SLL) experiencing disease progression on single ibrutinib. This study will evaluate the optimal ibrutinib dose (including doses higher than 420 mg) when combined with venetoclax
During the screening period, patients will continue on ibrutinib at their previous tolerated dose, unless required to stop (e.g.: by a preceding clinical trial).
On cycle 1, day 1, the dose of ibrutinib will be assigned based on the dose cohort. Patients in cohort 1 will receive ibrutinib 420 mg PO daily. Patients in cohort 2 will receive ibrutinib 560 mg PO daily. Cohort 3 will be 840 mg PO daily.
On cycle 1, day 1, patients will initiate venetoclax. The dose of venetoclax will ramp-up from 20 mg PO daily to 400 mg PO daily over a 5 week period.
The primary safety endpoint is determination of DLTs during the first 35 days (completion of dose ramp up). The primary efficacy endpoint of overall response rate will be assessed on approximately Cycle 7, Day 1.
Rationale: The optimal management of patients that progress on ibrutinib, including those with acquired Btk or PLCg2 mutations, is not determined. In other cancers, continued treatment with small molecule inhibitors beyond disease progression provides significant benefit, with additional agents or adjustments to ablate the resistant subclone. Venetoclax is approved for the treatment of patients with CLL, and is well-tolerated and effective in high-risk disease, and so is an appropriate agent for this trial.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
La Jolla, California, United States, 92093
- UC San Diego Moores Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Clinical and phenotypic verification of B cell CLL or SLL and measurable disease.
- Prior therapy: Patients must have been receiving single agent ibrutinib therapy at the time of disease progression. Patient may have received other therapy in combination with ibrutinib earlier in their treatment course.
- Women of childbearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study.
- Adequate hematologic, hepatic and renal function
Exclusion Criteria:
- Known CNS lymphoma or leukemia
- History of Richter's or prolymphocytic transformation.
- Primary ibrutinib resistance
- Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP)
- History of major surgery within 4 weeks prior to first dose on this study.
- History of prior malignancy, with the exception of adequately treated non-melanoma skin cancer, malignancies treated with curative intent and with no evidence of active disease for more than 3 years, or adequately treated cervical carcinoma in situ without current evidence of disease.
- Active clinically significant cardiovascular disease or history of myocardial infarction within 6 months of first dose.
- Active hepatitis B or C infection.
- Known history of infection with human immunodeficiency virus (HIV).
- Unable to swallow capsules or disease significantly affecting gastrointestinal function.
- History of stroke or intracranial hemorrhage within 6 months of first dose.
- Requires anticoagulation with warfarin or other Vitamin K antagonists.
- Requires treatment with a strong cytochrome P(CYP)450 3A inhibitor.
- Pregnant or breast-feeding women
- Current infection requiring parenteral antibiotics.
- Active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification.
- Patients who require immediate cytoreduction due to high risk of tumor lysis syndrome (ie, absolute lymphocyte count greater than 100k/uL).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: venetoclax with high-dose ibrutinib
venetoclax with high-dose ibrutinib for the treatment of patients with chronic lymphocytic leukemia with progressive disease on single agent ibrutinib.
|
On cycle 1, day 1, patients will initiate venetoclax.
The dose of venetoclax will ramp-up from 20 mg PO daily to 400 mg PO daily over a 5 week period.
Other Names:
During the screening period, patients will continue on ibrutinib at their previous tolerated dose, unless required to stop (e.g.: by a preceding clinical trial). On cycle 1, day 1, the dose of ibrutinib will be assigned based on the dose cohort. Patients in cohort 1 will receive ibrutinib 420 mg PO daily. Patients in cohort 2 will receive ibrutinib 560 mg PO daily. Cohort 3 will be 840 mg PO daily.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose or biologically active dose.
Time Frame: 1 year or more
|
Maximum tolerated dose or biologically active dose.
|
1 year or more
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment-emergent adverse events
Time Frame: 2 years or more
|
Treatment-emergent adverse events (description, timing, grade [CTCAE v4.03], severity, seriousness, and relatedness)
|
2 years or more
|
Overall response rate
Time Frame: 2 years or more
|
Partial Response, Partial Response with Lymphocytosis, and Complete Response) based on international working group guidelines.
Best overall response will be determined
|
2 years or more
|
Progression free survival rate at completion of combination therapy
Time Frame: 2 years or more
|
Progression free survival rate at completion of combination therapy, duration of response, as determined by International Working Group in CLL (iwCLL) criteria.
|
2 years or more
|
Stable disease rate
Time Frame: 2 years or more
|
Stable disease rate (also based on 2008 iwCLL guidelines), also at the time of primary endpoint response assessment.
|
2 years or more
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael Choi, MD, University of California, San Diego
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 171613
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Lymphocytic Leukemia
-
National Heart, Lung, and Blood Institute (NHLBI)Active, not recruitingLeukemia, Lymphocytic, Chronic, B-Cell | Chronic Lymphocytic Leukemia | Leukemia, Chronic Lymphatic | B-Cell Chronic Lymphocytic Leukemia | Leukemia, Lymphocytic, Chronic | B-Lymphocytic Leukemia, Chronic | Leukemia, Chronic Lymphocytic, B-Cell | Lymphocytic Leukemia, Chronic, B Cell | Lymphocytic Leukemia...United States
-
National Cancer Institute (NCI)CompletedB-cell Chronic Lymphocytic Leukemia | Refractory Chronic Lymphocytic Leukemia | Stage I Chronic Lymphocytic Leukemia | Stage II Chronic Lymphocytic Leukemia | Stage III Chronic Lymphocytic Leukemia | Stage IV Chronic Lymphocytic LeukemiaUnited States
-
National Cancer Institute (NCI)TerminatedRefractory Chronic Lymphocytic Leukemia | Stage I Chronic Lymphocytic Leukemia | Stage II Chronic Lymphocytic Leukemia | Stage III Chronic Lymphocytic Leukemia | Stage IV Chronic Lymphocytic LeukemiaUnited States
-
Mayo ClinicNational Cancer Institute (NCI)CompletedB-cell Chronic Lymphocytic Leukemia | Refractory Chronic Lymphocytic Leukemia | Stage 0 Chronic Lymphocytic Leukemia | Stage I Chronic Lymphocytic Leukemia | Stage II Chronic Lymphocytic LeukemiaUnited States
-
National Cancer Institute (NCI)CompletedB-cell Chronic Lymphocytic Leukemia | Stage I Chronic Lymphocytic Leukemia | Stage II Chronic Lymphocytic Leukemia | Stage III Chronic Lymphocytic Leukemia | Stage IV Chronic Lymphocytic LeukemiaUnited States
-
National Cancer Institute (NCI)TerminatedLeukemia | B-cell Chronic Lymphocytic Leukemia | Prolymphocytic Leukemia | Refractory Chronic Lymphocytic Leukemia | Stage I Chronic Lymphocytic Leukemia | Stage II Chronic Lymphocytic Leukemia | Stage III Chronic Lymphocytic Leukemia | Stage IV Chronic Lymphocytic LeukemiaUnited States
-
OHSU Knight Cancer InstituteOregon Health and Science UniversityCompletedRefractory Chronic Lymphocytic Leukemia | Stage I Chronic Lymphocytic Leukemia | Stage II Chronic Lymphocytic Leukemia | Stage III Chronic Lymphocytic Leukemia | Stage IV Chronic Lymphocytic LeukemiaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Celgene CorporationTerminatedChronic Lymphocytic Leukemia | B-cell Chronic Lymphocytic Leukemia | Stage 0 Chronic Lymphocytic Leukemia | Stage I Chronic Lymphocytic Leukemia | Stage II Chronic Lymphocytic LeukemiaUnited States
-
Roswell Park Cancer InstituteWithdrawnRefractory Chronic Lymphocytic Leukemia | Stage II Chronic Lymphocytic Leukemia | Stage III Chronic Lymphocytic Leukemia | Stage IV Chronic Lymphocytic Leukemia
-
Mayo ClinicNational Cancer Institute (NCI)CompletedChronic Lymphocytic Leukemia | Stage III Small Lymphocytic Lymphoma | Stage IV Small Lymphocytic Lymphoma | Stage 0 Chronic Lymphocytic Leukemia | Stage I Chronic Lymphocytic Leukemia | Stage II Chronic Lymphocytic Leukemia | Stage I Small Lymphocytic Lymphoma | Stage III Chronic Lymphocytic Leukemia and other conditionsUnited States
Clinical Trials on Venetoclax
-
Virginia Commonwealth UniversityAbbVieWithdrawnRelapsed Small Cell Lung Cancer | Refractory Small Cell Lung Carcinoma
-
PrECOG, LLC.Genentech, Inc.CompletedFollicular Lymphoma | Non-Hodgkin's Lymphoma Follicular | Non-Hodgkin's Lymphoma, Adult High GradeUnited States
-
University of Maryland, BaltimoreActive, not recruitingRelapsed or Refractory Acute Myeloid LeukemiaUnited States
-
Yale UniversityCompleted
-
Gruppo Italiano Malattie EMatologiche dell'AdultoRecruiting
-
Stichting Hemato-Oncologie voor Volwassenen NederlandNordic Lymphoma GroupActive, not recruiting
-
Stichting Hemato-Oncologie voor Volwassenen NederlandNordic CLL Study GroupActive, not recruitingChronic Lymphocytic Leukemia in Relapse | Chronic Lymphocytic Leukemia in RemissionNetherlands, Belgium, Denmark, Finland, Norway, Sweden
-
The Lymphoma Academic Research OrganisationInstitute of Cancer Research, United KingdomRecruitingMantle Cell LymphomaFrance, United Kingdom, Belgium
-
BioSight Ltd.Recruiting
-
National Heart, Lung, and Blood Institute (NHLBI)RecruitingChronic Lymphocytic LeukemiaUnited States