- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03534323
Duvelisib and Venetoclax in Relapsed or Refractory CLL or SLL or RS
A Phase I/II Study of Duvelisib and Venetoclax in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma or Patients With Richter's Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of an investigational drugs and also tries to define the appropriate dose of the investigational drugs to use for further studies. "Investigational" means that the drugs are being studied together for the first time.
This phase I study tests the safety of the drug duvelisib when used in combination with the drug venetoclax. Duvelisib is still being studied, but the FDA (the U.S. Food and Drug Administration) has approved the use of Duvelisib in patients with CLL/SLL with relapsed or refractory CLL after having received 2 or more prior therapies.
Duvelisib is a drug that is given in capsule form and taken by mouth. This drug is designed to stop cancer growth by blocking a protein called phosphatidylinositide 3-kinase (PI3K), which is important for the survival of CLL cells. In laboratory studies and in other clinical trials that included participants with CLL, duvelisib was effective at killing CLL cells.
Venetoclax is a tablet that is taken by mouth. Venetoclax targets a protein called BCL-2, which helps cancer cells survive. Venetoclax is an effective treatment for many participants with CLL who do not respond to chemotherapy or other approved drugs or who have relapsed after prior therapy.Venetoclax is FDA approved for participants with CLL who have never had therapy before or whose CLL has worsened after prior therapy.
In the phase I portion of this study, the investigators are looking to determine the dose of venetoclax that is safe to give with duvelisib and to see what the side effects are of this combination.
In the phase II portion of this study, we are looking to determine how effective thecombination of duvelisib and venetoclax is for patients with CLL or Richter's Syndrome
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Celeste Celeste
- Phone Number: 857-215-1646
- Email: celeste_carey@dfci.harvard.edu
Study Locations
-
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Florida
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Miami, Florida, United States, 33136
- Active, not recruiting
- University of Miami- Sylvester Comprehensive Cancer Center
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Maine
-
Brewer, Maine, United States, 04412
- Recruiting
- Northern Light Eastern Maine Medical Center
-
Contact:
- Bhandari Shruti, MD
-
Contact:
- Laurie Lewis
-
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Massachusetts
-
Boston, Massachusetts, United States, 02215
- Recruiting
- Dana Farber Cancer Institute
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Principal Investigator:
- Matthew S Davids, MD
-
Contact:
- Matthew Davids, MD
- Phone Number: 617-632-6331
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Boston, Massachusetts, United States, 02114
- Active, not recruiting
- Massachusetts General Hospital
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Boston, Massachusetts, United States, 02215
- Completed
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States, 02118
- Completed
- Boston Medical Center
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Pittsfield, Massachusetts, United States, 01201
- Completed
- Berkshire Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma requiring therapy, as per IW-CLL 2008 criteria OR Biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), consistent with Richter's Syndrome
- Disease that has progressed during or relapsed after at least one previous CLL/SLL therapy - If Richter's Syndrome, this criterion is not applicable
- Age greater to or equal to 18 years
- ECOG performance status ≤2 (Karnofsky ≥60%)
Patients must meet the following hematologic criteria at screening, unless they have significant bone marrow involvement of CLL confirmed on biopsy:
- Absolute neutrophil count ≥500 cells/mm3 (0.5 x 109/L). Growth factor is allowed in order to achieve this
- Platelet count ≥25,000 cells/mm3 (25 x 109/L) independent of transfusion within 7 days of screening
Adequate hepatic function defined as:
--Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN), bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
Adequate renal function as defined as:
--Serum creatinine ≤1.5 times the upper limit of normal or creatinine clearance ≥ 50 mL/min using a 24-hour urine collection
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method or abstinence) prior to study entry and for the duration of study participation
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Previous treatment with venetoclax or duvelisib
Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, surgery within 2 weeks of Cycle 1/Day 1 with the following exceptions:
- For patients on targeted therapies, a washout of least five half lives is required
- Patients who experience clinical deterioration may start therapy after a shorter washout period with prior approval by the PI
- Corticosteroid therapy (prednisone or equivalent <20 mg daily) is allowed
- Confirmed central nervous system involvement
- Allogeneic hematologic stem cell transplant within 6 months of starting study treatment or active graft vs. host disease (GVHD) requiring treatment or prophylaxis
- History of active malignancy requiring therapy with the exception of hormonal therapy
- Any active systemic infection requiring IV antibiotics or uncontrolled, active infections
- Known history of human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV)
- Major surgery within 4 weeks of first dose of study drug
- Currently active gastrointestinal disease, including colitis, inflammatory bowel disease and diarrhea requiring therapy
- Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk
- Use of Coumadin for anticoagulation (other anticoagulants permitted)
- Lactating or pregnant
- Concurrent administration of medications or foods that are strong inhibitors or inducers of CYP3A (see Appendix D) . The concomitant use of drugs or foods that are strong or moderate inhibitors or inducers of CYP3A are not allowed beginning 1 week prior to the first dose of duvelisib.
- Patients with ongoing use of prophylactic antibiotics are eligible as long as there is no evidence of active infection and the antibiotic is not included on the list of prohibited medications
- Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction resulting in malabsorption or chronic diarrhea
- Active abuse of alcohol
- History of chronic liver disease or veno-occlusive disease/sinusoidal obstruction syndrome
- History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function
- Known hypersensitivity to duvelisib and/or its excipients
- History of tuberculosis treatment within the 2 years prior to initiation of therapy
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: Duvelisib +Venetoclax,
Duvelisib will be given alone for the first seven days. On day 8 Venetoclax will be added.
|
This drug is designed to stop cancer growth by blocking a protein called phosphatidylinositide 3-kinase (PI3K), which is important for the survival of CLL cells.
Other Names:
Venetoclax targets a protein called BCL-2, which helps cancer cells survive.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose of Venetoclax When Administered with Duvelisib
Time Frame: Up to 7 weeks
|
As assessed by protocol-specified DLT criteria (phase I)
|
Up to 7 weeks
|
Rate of complete remission
Time Frame: 2 years
|
By IW-CLL criteria (phase II)
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cmax
Time Frame: Up to 7 weeks
|
Cmax
|
Up to 7 weeks
|
Half-life
Time Frame: Up to 7 weeks
|
Half-life
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Up to 7 weeks
|
Volume of Distribution
Time Frame: Up to 7 weeks
|
Volume of Distribution
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Up to 7 weeks
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Objective response rate
Time Frame: 2 years
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By IW-CLL Criteria
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2 years
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Duration of response
Time Frame: 2 years
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By IW-CLL Criteria
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2 years
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Progression free survival
Time Frame: 2 years
|
By IW-CLL Criteria
|
2 years
|
Rate of minimal residual disease negativity
Time Frame: 2 years
|
By IW-CLL Criteria
|
2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Matthew S Davids, MD, Dana-Farber Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
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
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Disease
- Leukemia, B-Cell
- Chronic Disease
- Syndrome
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Antineoplastic Agents
- Venetoclax
Other Study ID Numbers
- 18-089
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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.
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