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Clinical Trials (PDQ®)

Multi-center Trial of Revlimid® and Rituximab, for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL)

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IITreatmentActive18 and overOtherCRC014
Celgene # RV-CLL-PI-0223, NCT00628238

Trial Description

Summary

The study is a two-arm, multi-center trial of Revlimid® and Rituximab, for the frontline treatment of patients with Chronic Lymphocytic Leukemia (CLL) designed and conducted by the CLL Research Consortium (CRC). The purpose 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, and the significance of the tumor flare reaction. All patients will have assessment of known prognostic factors for CLL as well as novel prognostic factors will be evaluated for predicting response to treatment. Biologic corollary studies are designed to evaluate the mechanism of Revlimid® in CLL and the combination of Revlimid® and Rituximab.

Further Study Information

The CLL Research Consortium (CRC) is conducting a two-arm, multi-center phase II trial of Revlimid® and rituximab for the first-line treatment of patients with CLL.

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.

Eligibility Criteria

Inclusion Criteria:

1. Diagnosis of chronic lymphocytic leukemia with no history of previous treatments with monoclonal antibodies or chemotherapy.

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:

1. Previous treatment for CLL with chemotherapy or monoclonal antibodies

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Chronic Lymphocytic Leukemia Research Consortium

Celgene Corporation

Thomas J. KippsStudy Director

Danelle F James, M.D.Principal Investigator

Danelle F James, M.D.Ph: 858-822-7894
  Email: dfjames@ucsd.edu

Trial Sites

U.S.A.
California
  La Jolla
 Rebecca and John Moores UCSD Cancer Center
 Jamie N Gould Ph: 858-822-5364
  Email: jngould@ucsd.edu
 Danelle F James Ph: 858-822-7894
  Email: dfjames@ucsd.edu
 Thomas J. KippsPrincipal Investigator
 Danelle F James, M.D.Principal Investigator
Massachusetts
  Boston
 Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
 Evgeny Mikler, P.A. Ph: 617-632-4719
 Clinical Trials Office - Dana-Farber/Harvard Cancer Center Ph: 617-582-8480
 Jennifer Ruth BrownPrincipal Investigator
New York
  New Hyde Park
 Long Island Jewish Medical Center
 Nancy Driscoll, RPA-C Ph: 516-470-4767
  Email: Ndriscol@lij.edu
 Contact Person Ph: (516)470-4050
 Kanti Roop RaiPrincipal Investigator
Texas
  Houston
 M. D. Anderson Cancer Center at University of Texas
 Susan C Smith Ph: 713-745-0553
  Email: Susan Smith <scsmith@mdanderson.org>
 Clinical Trials Office Ph: 713-792-3245
 William G. WierdaPrincipal Investigator
 Michael J. KeatingPrincipal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00628238
ClinicalTrials.gov processed this data on August 01, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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