Rituximab, Lenalidomide, and Ibrutinib in Treating Patients With Previously Untreated Stage II-IV Follicular Lymphoma
A Phase I Study of Rituximab, Lenalidomide, and Ibrutinib in Previously Untreated Follicular Lymphoma
5 other identifiers
interventional
33
1 country
7
Brief Summary
This phase I trial studies the side effects and best dose of lenalidomide and ibrutinib when given together with rituximab in treating patients with previously untreated stage II-IV follicular lymphoma. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving lenalidomide and ibrutinib together with rituximab may work well in treating follicular lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2013
Longer than P75 for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 9, 2013
CompletedFirst Posted
Study publicly available on registry
April 11, 2013
CompletedStudy Start
First participant enrolled
June 26, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 11, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
June 6, 2026
ExpectedApril 13, 2026
December 1, 2025
1.9 years
April 9, 2013
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Maximally tolerated dose (MTD) of lenalidomide and ibrutinib for combination with rituximab
Defined as the highest dose at which 0 or 1 of 6 patients experience DLT. Will be determined by dose-limiting toxicities (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
28 days
Secondary Outcomes (5)
Toxicities by attribute and grade
Up to 10 years
Complete response rate
Up to 10 years
Overall response rate
Up to 10 years
Progression-free survival (PFS)
The time between registration and disease progression or death, assessed up to 10 years
Overall survival (OS)
The time between registration and death, assessed up to 10 years
Other Outcomes (2)
Pharmacokinetic parameters of ibrutinib and major metabolite PCI-45227
Days 1 and 15 of course 1 and week 13 (pre-dose, 1, 2, 4, 7, and 24 hours post-ibrutinib dose)
BTK parameters
At 4 hours and 24 hours post ibrutinib dosing
Study Arms (1)
Treatment (lenalidomide, ibrutinib, and rituximab)
EXPERIMENTALPatients 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 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 1, 8, 15, and 22 of cycle 1 and once weekly at weeks 13, 21, 29, and 37.
Interventions
Given PO
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- 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
- +38 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)lead
- Celgene Corporationcollaborator
Study Sites (7)
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Publications (2)
Rutherford SC, Yin J, Pederson L, Perez Burbano G, LaPlant B, Shadman M, Li H, LeBlanc ML, Kenkre VP, Hong F, Blum KA, Dockter T, Martin P, Jung SH, Grant B, Rosenbaum C, Ujjani C, Barr PM, Unger JM, Cheson BD, Bartlett NL, Kahl B, Friedberg JW, Mandrekar SJ, Leonard JP. Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials. J Clin Oncol. 2023 Jan 10;41(2):336-342. doi: 10.1200/JCO.21.02301. Epub 2022 Jul 5.
PMID: 35787017DERIVEDUjjani CS, Jung SH, Pitcher B, Martin P, Park SI, Blum KA, Smith SM, Czuczman M, Davids MS, Levine E, Lewis LD, Smith SE, Bartlett NL, Leonard JP, Cheson BD. Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103. Blood. 2016 Nov 24;128(21):2510-2516. doi: 10.1182/blood-2016-06-718106. Epub 2016 Oct 3.
PMID: 27697771DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Chaitra S Ujjani
Alliance for Clinical Trials in Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 9, 2013
First Posted
April 11, 2013
Study Start
June 26, 2013
Primary Completion
May 11, 2015
Study Completion (Estimated)
June 6, 2026
Last Updated
April 13, 2026
Record last verified: 2025-12