Multi-center Trial of Revlimid® and Rituximab, for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL)
NCT ID: NCT00628238
Last Updated: 2010-09-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE2
80 participants
INTERVENTIONAL
2008-02-29
2011-07-31
Brief Summary
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Detailed Description
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Revlimid® (lenalidomide) a derivative of thalidomide with immune-modulating properties. Revlimid® is FDA approved for treatment of relapsed multiple myeloma and 5q- myelodysplastic syndrome. Revlimid® has promising clinical activity in relapsed CLL in two early clinical trials. However, the mechanism(s) whereby Revlimid® is active in CLL is unknown. Rituximab (Rituxan®) is a protein that binds to CD20 expressed on normal and leukemia B cells. Rituximab is FDA approved for the treatment of lymphoma and is used commonly for the treatment of CLL. The purposes of this study are to evaluate the safety and activity of the combination of Revlimid® and rituximab in CLL, elucidate the mechanism of Revlimid® in CLL, and to assess whether prognostic factors might predict those patients likely to benefit from this therapy in the future.
As older patients are commonly under-represented in CLL clinical trials and are less tolerable of frontline therapy that utilizes combinations of fludarabine and cyclophosphamide the trial has two arms; one to specifically assess for the tolerability of the regimen in older subjects.
The primary objective of this study is to determine the response rate of the combination of Revlimid® and Rituximab in previously untreated CLL patients in two arms- those aged 65 years and above and those younger than 65. Secondary objectives will evaluate the safety of the combination of Revlimid® and Rituximab, response duration, improvement in hematologic parameters, activity of the combination in high-risk CLL subsets, and the significance of the tumor flare reaction.
All patients will have baseline assessment of known CLL prognostic factors including: immunoglobulin variable heavy chain (IgVH) gene mutational status, interphase cytogenetics, intracellular ZAP-70 expression, and CD38 expression through the CRC tissue core. These known prognostic features in CLL together with novel prognostic factors will be evaluated for the ability to predict response to treatment with Revlimid® and the combination of Revlimid® and Rituximab. Extensive biologic corollary studies are designed to evaluate the mechanism of Revlimid® in CLL, the impact of Revlimid® on the CLL microenvironment, and Revlimid®'s impact on and rituximab mediated cytotoxicity.
All patients will receive the same treatment. Revlimid® will be started at a low dose and slowly escalated based on patient tolerability. Rituximab will be administered following 21 days of Revlimid® monotherapy. Patients will continue treatment for up to 7 cycles unless there is toxicity or progressive disease. There are three planned response assessments for the subjects: a single agent Revlimid® response assessment prior to the addition of rituximab, after 3 cycles of treatment, and following all the therapy.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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A
Subjects younger than 65 years old.
Lenalidomide and Rituximab
Lenalidomide starting at a low dose and escalated based on patient tolerability 21 days of every cycle. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles. Each patient may receive up to a maximum of 7 cycles of treatment if no progressive disease or significant toxicity.
B
Subjects aged 65 years and older
Lenalidomide and Rituximab
Lenalidomide starting at a low dose and escalated based on patient tolerability 21 days of every cycle. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles. Each patient may receive up to a maximum of 7 cycles of treatment if no progressive disease or significant toxicity.
Interventions
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Lenalidomide and Rituximab
Lenalidomide starting at a low dose and escalated based on patient tolerability 21 days of every cycle. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles. Each patient may receive up to a maximum of 7 cycles of treatment if no progressive disease or significant toxicity.
Lenalidomide and Rituximab
Lenalidomide starting at a low dose and escalated based on patient tolerability 21 days of every cycle. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles. Each patient may receive up to a maximum of 7 cycles of treatment if no progressive disease or significant toxicity.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Subjects must have an indication for treatment as defined by the NCI Working Group Guidelines
3. Understand and voluntarily sign an informed consent form.
4. Age ≥18 years at the time of signing the informed consent form.
5. Able to adhere to the study visit schedule and other protocol requirements.
6. ECOG performance status of ≤ 2 at study entry (see Appendix A).
7. Laboratory test results within these ranges: Absolute neutrophil count ≥ 1.0 x 109/L, Platelet count ≥ 50 x 109/L, Serum creatinine ≤ 1.5 mg/dL, Total bilirubin ≤ 1.5 mg/dL, AST \& ALT ≤ 2 x ULN
8. Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and 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 she starts taking 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. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
9. Disease free of prior malignancies for ≥ 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast
Exclusion Criteria
2. Known Hepatitis B Ag positive, Hepatitis C positive patients
3. Known HIV positive patients
4. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
5. Inability to provide informed consent.
6. Concurrent malignancy (excluding basal and squamous cell skin cancers).
7. Active fungal, bacterial, and/or viral infection.
8. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
9. Pregnant or breast-feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
10. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
11. Use of any other experimental drug or therapy within 28 days of baseline.
12. Known hypersensitivity to thalidomide.
13. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
14. Any prior use of lenalidomide.
15. Concurrent use of other anti-cancer agents or treatments.
16. Patients with history of deep venous thrombus or pulmonary embolism. Patients who are at increased risk of thrombosis during treatment with lenalidomide including those taking concurrent erythropoietin, darbepoetin or high-dose corticosteroids are also excluded.
17. Patients with a history of embolic events (e.g. TIA) from arrhythmia or peripheral arterial disease or of recent MI whether or not treated with anti-platelet drugs
ALL
No
Sponsors
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Celgene Corporation
INDUSTRY
Chronic Lymphocytic Leukemia Research Consortium
NETWORK
Responsible Party
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Chronic Lymphocytic Leukemia Research Consortium (CRC)
Principal Investigators
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Thomas J Kipps, M.D., Ph.D
Role: STUDY_DIRECTOR
Director of the CLL Research Consortium and University of California San Diego
Danelle F James, M.D.
Role: PRINCIPAL_INVESTIGATOR
CLL Research Consortium and University of California San Diego
Locations
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University of California San Diego
La Jolla, California, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States
Long Island Jewish Medical Center
New Hyde Park, New York, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
Columbus, Ohio, United States
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States
Countries
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Central Contacts
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Facility Contacts
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Evgeny Mikler, P.A.
Role: primary
Clinical Trials Office - Dana-Farber/Harvard Cancer Center
Role: backup
Role: backup
Clinical Trials Office - OSU Comprehensive Cancer Center
Role: primary
Clinical Trials Office
Role: backup
References
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Chanan-Khan A, Miller KC, Musial L, Lawrence D, Padmanabhan S, Takeshita K, Porter CW, Goodrich DW, Bernstein ZP, Wallace P, Spaner D, Mohr A, Byrne C, Hernandez-Ilizaliturri F, Chrystal C, Starostik P, Czuczman MS. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. J Clin Oncol. 2006 Dec 1;24(34):5343-9. doi: 10.1200/JCO.2005.05.0401. Epub 2006 Nov 6.
Chanan-Khan A, Porter CW. Immunomodulating drugs for chronic lymphocytic leukaemia. Lancet Oncol. 2006 Jun;7(6):480-8. doi: 10.1016/S1470-2045(06)70723-9.
Ferrajoli A, Lee BN, Schlette EJ, O'Brien SM, Gao H, Wen S, Wierda WG, Estrov Z, Faderl S, Cohen EN, Li C, Reuben JM, Keating MJ. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood. 2008 Jun 1;111(11):5291-7. doi: 10.1182/blood-2007-12-130120. Epub 2008 Mar 11.
Related Links
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Website for the CLL Research Consortium
Moore's UCSD Cancer Center
Other Identifiers
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Celgene # RV-CLL-PI-0223
Identifier Type: -
Identifier Source: secondary_id
CRC014
Identifier Type: -
Identifier Source: org_study_id