- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02532257
Ibrutinib in Combination With Rituximab and Lenalidomide in Treating Patients With Previously Untreated, Stage II-IV Follicular Lymphoma or Marginal Zone Lymphoma
An Open Label, Phase 2 Study of Ibrutinib in Combination With Rituximab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma and Marginal Zone Lymphoma
Study Overview
Status
Conditions
- CD20 Positive
- Ann Arbor Stage II Follicular Lymphoma
- Ann Arbor Stage III Follicular Lymphoma
- Ann Arbor Stage IV Follicular Lymphoma
- Grade 1 Follicular Lymphoma
- Grade 2 Follicular Lymphoma
- Grade 3a Follicular Lymphoma
- Ann Arbor Stage II Marginal Zone Lymphoma
- Ann Arbor Stage III Marginal Zone Lymphoma
- Ann Arbor Stage IV Marginal Zone Lymphoma
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in patients with previously untreated follicular lymphoma (FL) and marginal zone lymphoma (determined by progression-free survival at 2 years).
SECONDARY OBJECTIVES:
I. To evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in subjects with FL as assessed by complete response rate (CR) at 120 weeks, overall response rate (ORR), duration of response (DOR), event free survival (EFS), time to next anti-lymphoma treatment (TTNT), and overall survival (OS).
II. To evaluate the safety and tolerability of ibrutinib combined with rituximab and lenalidomide in previously untreated subjects with FL and marginal zone lymphoma.
EXPLORATORY OBJECTIVES:
I. To evaluate prognostic and mechanistic biomarkers relative to treatment outcomes.
OUTLINE:
Patients receive lenalidomide orally (PO) on days 1-21, rituximab intravenously (IV) over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for 1 year and then every 24 weeks for 2 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologically confirmed CD20+ follicular lymphoma, grade 1, 2, or 3a or marginal zone lymphoma
- Have had no prior systemic treatment for lymphoma
- Bi-dimensionally measurable disease, with at least one mass lesion >= 2 cm in longest diameter by computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI)
- In the opinion of the investigator would benefit from systemic therapy
- Stage II, III, or IV disease
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Absolute neutrophil count (ANC) >= 1,000/mm^3, independent of growth factor support (within 28 days prior to signing informed consent).
- Platelet counts >= 100,000/mm^3 or >= 50,000/mm^3 if bone marrow involvement with lymphoma, independent of transfusion support in either situation (within 28 days prior to signing informed consent).
- Serum aspartate transaminase (AST) or alanine transaminase (ALT) < 3 x upper limit of normal (ULN)
- Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula
- Bilirubin < 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL
- Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN
- Must be able to adhere to the study visit schedule and other protocol requirements
- Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study; females of childbearing potential: must either completely abstain from heterosexual sexual conduct or must use 2 methods of reliable contraception, 1 highly effective (intrauterine device, birth control pills, hormonal patches, injections, vaginal rings, or implants) and at least 1 additional method (condom, diaphragm, cervical cap) of birth control; reliable contraceptive methods must be started at least 4 weeks before lenalidomide; males who are sexually active must be practicing complete abstinence or agree to a condom during sexual contact with a pregnant female or female of child bearing potential; men must agree to not donate sperm during and after the study; for females, these restrictions apply at least 4 weeks before study treatment, during the period of therapy and for 1 month after the last dose of study drug; for males, these restrictions apply during the period of therapy and for 3 months after the last dose of study drug
- Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [Beta-hCG]) pregnancy test at screening; women who are pregnant or breastfeeding are ineligible for this study; females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program
- Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
- All study participants must be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the REMS program
Exclusion Criteria:
- Known central nervous system lymphoma or leptomeningeal disease, except subjects with a history of central nervous system lymphoma treated and in remission > 6 months
- Evidence of diffuse large B-cell transformation
- Grade 3b FL
Any prior history of other malignancy besides FL or marginal zone lymphoma, unless the patient has been free of disease for >= 5 years and felt to be at low risk for recurrence by the treating physician, except:
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk, including but not limited to:
- Moderate to severe hepatic impairment (Child-Pugh classes B and C)
Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection, or any uncontrolled active systemic infection
- Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated
- Prior use of ibrutinib or other BTK inhibitors, rituximab or lenalidomide
- Concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration glucocorticoid equivalent of > 10 mg/day of prednisone) within 28 days of the first dose of study drug
- Known anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon); if patients have been on warfarin or equivalent vitamin K antagonists in the past, they will not be eligible if administered within 30 days of the first dose of study drug
- Requires chronic treatment with strong CYP3A inhibitors; if patients have been on a strong CYP3A inhibitor in the past, they will not be eligible if the CYP3A inhibitor was administered within 7 days of the first dose of study drug
- Requires chronic treatment with strong CYP3A inducers, for a list of strong CYP3A inducers, see the protocol. If patients have been on a strong CYP3A inducer in the past, they will not be eligible if the CYP3A inducer was administered within 7 days of the first dose of study drug
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional classification
- Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block
- Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia
- History of stroke or intracranial hemorrhage within 6 months prior to study entry
- Vaccinated with live, attenuated vaccines within 4 weeks of study entry
- Lactating or pregnant subjects
- Administration of any investigational agent within 28 days of first dose of study drug
- Patients who have undergone major surgery within 7 days or minor surgery within 3 days of first dose of study drug
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: Treatment (lenalidomide, rituximab, ibrutinib)
Patients receive lenalidomide PO on days 1-21, rituximab IV over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO QD on days 1-28.
Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival (PFS)
Time Frame: Time from the treatment start date (course 1, day 1) until thefirst date of objectively documented progressive disease or date of death from any cause, assessed for up to 2 years
|
Response will be assessed by the investigator based on the 2014 Cheson Lugano criteria.
The 2-year PFS rate will be calculated and corresponding 95% confidence interval (CI) will be derived.
Kaplan-Meier method will be used to estimate the PFS.
Corresponding 95% CI will be summarized.
Cox proportional hazards models will be used to assess the effects of patient prognostic factors on time-to-event endpoints.
|
Time from the treatment start date (course 1, day 1) until thefirst date of objectively documented progressive disease or date of death from any cause, assessed for up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete response (CR) rate
Time Frame: At 120 weeks
|
Will be defined as the percentage of subjects with a CR at 120 weeks as determined by the principal investigator (Cheson, Lugano classification 2014).
|
At 120 weeks
|
Overall response rate (ORR) (CR rate + partial response [PR])
Time Frame: Up to 3 years
|
Will be defined as the percentage of subjects with an ORR and assessed by the investigator based on Cheson, Lugano 2014.
The best ORR will be recorded.
|
Up to 3 years
|
Duration of response (DOR)
Time Frame: Time by which measurement criteria for CR rate or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented; assessed up to 3 years
|
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
|
Time by which measurement criteria for CR rate or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented; assessed up to 3 years
|
Event free survival (EFS)
Time Frame: From the date of course 1, day 1 to the date of first documented progression, transformation to diffuse large B-cell lymphoma, initiation of new anti-lymphoma treatment, or death; assessed up to 3 years
|
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
|
From the date of course 1, day 1 to the date of first documented progression, transformation to diffuse large B-cell lymphoma, initiation of new anti-lymphoma treatment, or death; assessed up to 3 years
|
Time to next anti-lymphoma treatment (TTNT)
Time Frame: From the date of course 1, day 1 to the date of first documented administration of any anti-lymphoma treatment (chemotherapy, radiotherapy, immune therapy, radioimmunotherapy, or other experimental therapy); assessed up to 3 years
|
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
|
From the date of course 1, day 1 to the date of first documented administration of any anti-lymphoma treatment (chemotherapy, radiotherapy, immune therapy, radioimmunotherapy, or other experimental therapy); assessed up to 3 years
|
Overall survival (OS)
Time Frame: From the date of course 1, day 1 to the date of death regardless of cause; assessed up to 3 years
|
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
|
From the date of course 1, day 1 to the date of death regardless of cause; assessed up to 3 years
|
Frequency (number and percentage) of treatment-emergent adverse events (AEs)
Time Frame: Up to 3 years
|
Additional AE summaries will include AE frequency by AE severity and by relationship to study drug.
|
Up to 3 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Loretta J Nastoupil, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
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
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma, B-Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell, Marginal Zone
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Antibodies
- Lenalidomide
- Immunoglobulins
- Rituximab
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
Other Study ID Numbers
- 2015-0361 (Other Identifier: M D Anderson Cancer Center)
- NCI-2015-01513 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
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 CD20 Positive
-
Sunshine Guojian Pharmaceutical (Shanghai) Co.,...Unknown
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedHematopoietic and Lymphoid Cell Neoplasm | Lymphoma | CD20 Positive | Lymphocytic NeoplasmUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)WithdrawnMantle Cell Lymphoma | CCND1 Positive | CD20-Positive Neoplastic Cells Present
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingRecurrent Mantle Cell Lymphoma | Mantle Cell Lymphoma | CCND1 Positive | CCND2 Positive | CCND3 Positive | CD20 Positive | Refractory Mantle Cell LymphomaUnited States
-
Mentrik Biotech, LLCUnknownPreviously Treated CD20+ B-cell MalignanciesUnited States
-
Poitiers University HospitalCompleted
-
Guangzhou Excelmab Inc.RecruitingSafety and Efficacy of EX103 in Subjects With Relapsed/Refractory CD20-Positive Non-Hodgkin LymphomaCD20-positive Non-Hodgkin LymphomaChina
-
Conjupro Biotherapeutics, Inc.SuspendedCD20 Positive Non Hodgkin LymphomaUnited States
-
Seoul National University HospitalGyeongsang National University Hospital; Hallym University Medical Center; Kyunghee...TerminatedCD20-positive Non-Hodgkin LymphomaKorea, Republic of
-
Maria Sklodowska-Curie National Research Institute...KCRINot yet recruitingCD20-positive Acute Lymphoblastic LeukemiaPoland
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Monoblastic Leukemia (M5a) | Childhood Acute Monocytic Leukemia (M5b) | Childhood Acute Myeloblastic Leukemia Without Maturation (M1) | Childhood Acute Myelomonocytic Leukemia (M4) | Childhood Acute Myeloid Leukemia/Other Myeloid MalignanciesUnited States