- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02956382
Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
District of Columbia
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Washington, District of Columbia, United States, 20007
- Georgetown Lombardi Comprehensive Cancer Center
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New Jersey
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Hackensack, New Jersey, United States, 07601
- John Theurer Cancer Center at Hackensack University Medical Center
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Washington
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Seattle, Washington, United States, 98109
- Seattle Cancer Care Alliance
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Relapsed or refractory, histologically confirmed follicular lymphoma, grade I, II, or IIIa which requires therapy defined by at least one of the following:
- Constitutional symptoms
- Cytopenias
- High tumor burden (single mass > 7 cm, three masses > 3 cm, symptomatic splenomegaly, organ compression or compromise, ascites, pleural effusion)Must have received at least two prior systemic therapies
- All risk by FLIPI 0-5 factors (Appendix I)
Measurable disease Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable. Any tumor mass > 1.5 cm is acceptable.
Lesions that are considered non-measurable include the following:
- Bone lesions (lesions if present should be noted)
- Ascites
- Pleural/pericardial effusion
- Lymphangitis cutis/pulmonis
- Bone marrow (involvement by lymphoma should be noted)
Adequate hematologic function independent of transfusion and growth factor support for at least 3 weeks prior to screening unless attributable to disease. Defined as:
- Absolute neutrophil count (ANC) >1000 cells/mm3 (1.0 x 109/L). ANC > 500 cells/mm3 is permissible if due to disease.
- Platelet count >50,000 cells/mm3 (50 x 109/L) unless attributable to disease. Platelet count > 20,000 cells/mm3 is permissible if due to disease.
- Hemoglobin >8.0 g/dL.
Adequate hepatic and renal function defined as:
- Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 5 is permissible if due to disease.
- Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) Bilirubin ≤3 x ULN is permissible if due to disease.
- Estimated Creatinine Clearance ≥50 ml/min (Cockcroft-Gault based on actual weight)
- Prothrombin time (PT)/International normalized ratio (INR) <1.5 x ULN and PTT (aPTT) <1.5 x ULN.
- Men and women ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. (Appendix II)
- Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
- Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence, or sterilized partner) during the period of therapy and for 30 days after the last dose of study drug
Exclusion Criteria:
- Chemotherapy, monoclonal antibody, or small molecule kinase inhibitor less than or equal 21 days prior to first administration of study treatment
- Prior exposure to a Bruton's tyrosine kinase (BTK) or B-cell lymphoma 2 (BCL-2) inhibitor.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib or venetoclax.
- Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects at risk for tumor lysis syndrome.
History of other malignancies, except:
- Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease.
- Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration [>14 days] of > 20 mg/day of prednisone) within 28 days of the first dose of study drug.
- Undergone an allogeneic stem cell transplant within the past 1 year.
- Current or history of graft versus host disease
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.
- Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.03), grade ≤1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia.
- Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Known HIV infection
Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
• Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, hepatitis C antibody, must have a negative polymerase chain reaction (PCR) result for the respective disease before enrollment. Those who are PCR positive will be excluded.
- Any uncontrolled active systemic infection.
- Major surgery within 4 weeks of first dose of study drug.
- 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.
- 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.
- Unable to swallow capsules or tablets 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.
- Concomitant use of warfarin or other Vitamin K antagonists.
- Requires treatment with a strong cytochrome P450 CYP3A4/5 inhibitor. (Appendix V)
- Richter's transformation confirmed by biopsy.
- Malabsorption syndrome or other condition precluding enteral route of administration.
- Known Central nervous system (CNS) involvement by lymphoma
- Erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome
- Lactating or pregnant.
- Unwilling or unable to participate in all required study evaluations and procedures.
- Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
- Currently active, clinically significant hepatic impairment (greater than or equal moderate hepatic impairment according to the Child Pugh classification (see Appendix IX)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase I - Dose Level 0
Ibrutinib (capsule) - 420mg Venetoclax (tablet) - 400mg Each medication is taken daily. Treatment cycles are 28 days long. |
Ibrutinib is dispensed as a capsule.
Other Names:
Venetoclax is dispensed as a tablet.
Other Names:
|
Experimental: Phase I - Dose Level 1
Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 400mg Each medication is taken daily. Treatment cycles are 28 days long. |
Ibrutinib is dispensed as a capsule.
Other Names:
Venetoclax is dispensed as a tablet.
Other Names:
|
Experimental: Phase I - Dose Level 2
Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 600mg Each medication is taken daily. Treatment cycles are 28 days long. |
Ibrutinib is dispensed as a capsule.
Other Names:
Venetoclax is dispensed as a tablet.
Other Names:
|
Experimental: Phase I - Dose Level 3
Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 800mg Each medication is taken daily. Treatment cycles are 28 days long. |
Ibrutinib is dispensed as a capsule.
Other Names:
Venetoclax is dispensed as a tablet.
Other Names:
|
Experimental: Phase II Dose
The Phase II dose will be the maximum tolerated dose as determined in the Phase I portion.
|
Ibrutinib is dispensed as a capsule.
Other Names:
Venetoclax is dispensed as a tablet.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Recommended Phase 2 dose
Time Frame: 18 months
|
The maximum tolerated dose of Ibrutinib and Venetoclax
|
18 months
|
Response Rate
Time Frame: 36 months
|
Response rate seen in the combination versus 30% response rate for current individual therapies for this group of patients
|
36 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics of Ibrutinib
Time Frame: 18 months
|
Steady-state plasma concentrations of ibrutinib
|
18 months
|
Pharmacokinetics of Venetoclax
Time Frame: 18 months
|
Steady-state plasma concentrations of venetoclax
|
18 months
|
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time Frame: 36 months
|
Toxicity (attribute and grade) will be summarized for each dose level for all patients who receive at least one dose of study treatment
|
36 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Chaitra Ujjani, MD, Seattle Cancer Care Alliance
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 (Estimate)
Study Record Updates
Last Update Posted (Estimate)
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
- 2016-0014
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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