Rituximab, Lenalidomide, and Ibrutinib in Treating Patients With Previously Untreated Stage II-IV Follicular Lymphoma
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01829568 |
Recruitment Status :
Active, not recruiting
First Posted : April 11, 2013
Last Update Posted : February 17, 2021
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Ann Arbor Stage II Grade 1 Contiguous Follicular Lymphoma Ann Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma Ann Arbor Stage II Grade 2 Contiguous Follicular Lymphoma Ann Arbor Stage II Grade 2 Non-Contiguous Follicular Lymphoma Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma Ann Arbor Stage II Grade 3 Non-Contiguous Follicular Lymphoma Ann Arbor Stage III Grade 1 Follicular Lymphoma Ann Arbor Stage III Grade 2 Follicular Lymphoma Ann Arbor Stage III Grade 3 Follicular Lymphoma Ann Arbor Stage IV Grade 1 Follicular Lymphoma Ann Arbor Stage IV Grade 2 Follicular Lymphoma Ann Arbor Stage IV Grade 3 Follicular Lymphoma | Drug: Ibrutinib Other: Laboratory Biomarker Analysis Drug: Lenalidomide Other: Pharmacological Study Biological: Rituximab | Phase 1 |
PRIMARY OBJECTIVES:
I. To determine the recommended phase II doses of ibrutinib and lenalidomide for combination with rituximab in previously untreated follicular lymphoma.
SECONDARY OBJECTIVES:
I. To determine pharmacokinetics of ibrutinib and its major metabolite (PCI-45227) when combined with lenalidomide and rituximab.
II. To determine the pharmacodynamics of basophil activation and Bruton tyrosine kinase (BTK) occupancy in peripheral blood mononuclear cells (PBMCs) over a 24-hour period of ibrutinib when given in combination with lenalidomide and rituximab.
OUTLINE: This is a dose-escalation study of lenalidomide and ibrutinib.
Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21 and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab intravenously (IV) on days 1, 8, 15, and 22 of course 1 and once weekly at weeks 13, 21, 29, and 37.
After completion of study treatment, patients are followed up every 4 months for 2 years and then every 6 months for 8 years or every 6 months or annually for 10 years.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 33 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I Study of Rituximab, Lenalidomide, and Ibrutinib in Previously Untreated Follicular Lymphoma |
Actual Study Start Date : | June 21, 2013 |
Actual Primary Completion Date : | May 11, 2015 |
Arm | Intervention/treatment |
---|---|
Experimental: Treatment (lenalidomide, ibrutinib, and rituximab)
Patients receive lenalidomide PO QD on days 1-21 and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and once weekly at weeks 13, 21, 29, and 37.
|
Drug: Ibrutinib
Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Lenalidomide Given PO
Other Names:
Other: Pharmacological Study Correlative studies Biological: Rituximab Given IV
Other Names:
|
- Maximally tolerated dose (MTD) of lenalidomide and ibrutinib for combination with rituximab, determined by dose-limiting toxicities (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ]Defined as the highest dose at which 0 or 1 of 6 patients experience DLT.
- Toxicities by attribute and grade, assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 10 years ]Summarized for each dose level.
- Complete response rate [ Time Frame: Up to 10 years ]Estimated for each dose level.
- Overall response rate [ Time Frame: Up to 10 years ]Estimated for each dose level.
- Progression-free survival (PFS) [ Time Frame: The time between registration and disease progression or death, assessed up to 10 years ]Estimated by Kaplan-Meier method for the whole number of patients in this study and at the MTD.
- Overall survival (OS) [ Time Frame: The time between registration and death, assessed up to 10 years ]Estimated by Kaplan-Meier method for the whole number of patients in this study and at the MTD.
- Pharmacokinetic parameters of ibrutinib and major metabolite PCI-45227 [ Time Frame: Days 1 and 15 of course 1 and week 13 (pre-dose, 1, 2, 4, 7, and 24 hours post-ibrutinib dose) ]Tabulated and summarized using descriptive statistics.
- BTK parameters [ Time Frame: At 4 hours and 24 hours post ibrutinib dosing ]Tabulated and summarized using descriptive statistics.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
-
Previously untreated, histologically confirmed follicular lymphoma, World Health Organization (WHO) classification grade I, II, or IIIa (> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass >= 7 cm in any unidimensional measurement) stage II and requires therapy at the discretion of the primary physician
- Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine needle aspirates are not acceptable for diagnosis
- Failure to submit pathology specimens within 60 days of patient registration will be considered a major protocol violation
- Institutional flow cytometry or immunohistochemistry must confirm cluster of differentiation 20 (CD20) antigen expression
- All risk by follicular lymphoma international prognostic index (FLIPI): 0-5 risk factors
- No prior systemic therapy for non-Hodgkin lymphoma (NHL) including chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy), radiation therapy, or radioimmunotherapy
- For non-NHL conditions, no chemotherapy, radiotherapy, or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of enrollment; no patients who have ongoing adverse events from agents administered more than 4 weeks previously
- No prior exposure to any of the study agents
- No corticosteroids within two weeks prior to study entry, except for maintenance therapy for a non-malignant disease; dose of corticosteroid or prednisone (or its equivalent) should not exceed 20 mg per day; corticosteroid premedication for rituximab is allowed
- Eastern Cooperative Oncology Group (ECOG) performance status must be =< 2
-
Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 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 NHL should be noted)
-
Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following:
- No evidence of coinfection with hepatitis B or C
- CD4+ cell count >= 400/mm^3
- No evidence of resistant strains of HIV
- If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV ribonucleic acid (RNA)/mL
- If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL
- No history of acquired immunodeficiency syndrome (AIDS)-defining conditions
- No use of strong cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) inhibitors or inducers
- No known central nervous system (CNS) involvement by lymphoma
- No treatment with strong inhibitors or inducers of CYP3A4/5
- No evidence of active hepatitis B or C infections (i.e., no positive serology for anti-hepatitis B virus [HBV] or anti-hepatitis C virus [HCV] antibodies); HBV seropositive patients (hepatitis B surface antigen [HBsAg] +) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxyribonucleic acid (DNA) testing and receive suppressive therapy with lamivudine or other HBV suppressive therapy until 6 months after the last rituximab dose
- No history of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome
- No history of uncontrolled seizures
- No autoimmune disorder that requires active immunosuppression
- No intracranial hemorrhage within the last 6 months
- Non-pregnant and non-nursing; females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy, or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time preceding 24 consecutive months)
- No known human anti-chimeric antibody (HACA) positivity
- No anticoagulation with warfarin is allowed; patients must not have received warfarin within 28 days prior to registration; alternative anticoagulant may be used
- Patients must not be receiving concurrent treatment with other investigational drugs
- Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide, ibrutinib, or other agents used in study
- Patients must not have presence of transfusion-dependent thrombocytopenia
-
No currently active clinically significant cardiovascular disease including the following:
- No uncontrolled arrhythmia
- No congestive heart failure
- No class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- No history of myocardial infarction, deep venous or arterial thrombosis within 6 months prior to registration
-
No prior malignancy with the exceptions listed below:
- Malignancy treated with curative intent and with no evidence of active disease for more than 3 years prior to screening and felt to be at low risk for recurrence by the treating physician
- Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
- Adequately treated cervical carcinoma in situ without current evidence of disease
- Absolute neutrophil count (ANC) >= 1,000/microliter
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
- Total bilirubin =< 1.5 x ULN unless attributable to NHL; unless attributable to Gilbert's syndrome
- Creatinine clearance > 60 mL/min (patients on dialysis are not eligible); to be calculated by method of Cockcroft-Gault, using actual weight
- Creatinine =< 2 x ULN
- Platelet count >= 75,000/microliter

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01829568
United States, District of Columbia | |
MedStar Georgetown University Hospital | |
Washington, District of Columbia, United States, 20007 | |
United States, Illinois | |
University of Chicago Comprehensive Cancer Center | |
Chicago, Illinois, United States, 60637 | |
United States, Massachusetts | |
Dana-Farber Cancer Institute | |
Boston, Massachusetts, United States, 02215 | |
United States, New York | |
Roswell Park Cancer Institute | |
Buffalo, New York, United States, 14263 | |
NYP/Weill Cornell Medical Center | |
New York, New York, United States, 10065 | |
United States, North Carolina | |
UNC Lineberger Comprehensive Cancer Center | |
Chapel Hill, North Carolina, United States, 27599 | |
United States, Ohio | |
Ohio State University Comprehensive Cancer Center | |
Columbus, Ohio, United States, 43210 |
Principal Investigator: | Chaitra S Ujjani | Alliance for Clinical Trials in Oncology |
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT01829568 |
Other Study ID Numbers: |
NCI-2013-00792 NCI-2013-00792 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) A051103 CALGB-A051103 A051103 ( Other Identifier: Alliance for Clinical Trials in Oncology ) A051103 ( Other Identifier: CTEP ) U10CA180821 ( U.S. NIH Grant/Contract ) U10CA031946 ( U.S. NIH Grant/Contract ) |
First Posted: | April 11, 2013 Key Record Dates |
Last Update Posted: | February 17, 2021 |
Last Verified: | December 2020 |
Lymphoma Lymphoma, Follicular Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Rituximab Antineoplastic Agents, Immunological Lenalidomide |
Antibodies Immunoglobulins Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents Antirheumatic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |