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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Chronic Lymphocytic Leukemia Research Consortium.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Celgene Corporation
Information provided by:
Chronic Lymphocytic Leukemia Research Consortium
ClinicalTrials.gov Identifier:
NCT00628238
First received: February 26, 2008
Last updated: September 8, 2010
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
CLL
Untreated
Front-line
First-Line
Initial Therapy
Drug: Lenalidomide and Rituximab
Phase 2

Chronic Lymphocytic Leukemia Research Consortium has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two-Arm, Multi-center Trial of Revlimid® and Rituximab, for First-Line Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL)

Resource links provided by NLM:


Further study details as provided by Chronic Lymphocytic Leukemia Research Consortium:

Primary Outcome Measures:
  • Efficacy to be assessed by clinical response rate following 3 cycles of treatment and the NCI-CLL working group response rate assessed after completion of all treatment. [ Time Frame: clinical response assessment after 3 cycles of therapy and 3 months following completion of all therapy for NCI-CLL working group response assessment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety - type, frequency, severity, and relationship of adverse events to study treatment [ Time Frame: Throughout the study period ] [ Designated as safety issue: Yes ]
  • Time To Progression [ Time Frame: Following therapy until disease progression ] [ Designated as safety issue: No ]
  • Evaluate response to lenalidomide in relationship to molecular and genetic prognostic features in CLL; including ZAP-70 status, IgVH gene mutational status, and FISH. [ Time Frame: Following final response assessment ] [ Designated as safety issue: No ]
  • Compare the efficacy and tolerability of the combination of Revlimid and rituximab for patients younger than 65 years, and for those 65 and older. • [ Time Frame: following final response assessment ] [ Designated as safety issue: No ]
  • Evaluate change in hematological parameters including neutropenia, anemia, and thrombocytopenia following treatment with the combination of Revlimid and rituximab. [ Time Frame: Following final response assessment ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: February 2008
Estimated Study Completion Date: July 2011
Estimated Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Subjects younger than 65 years old.
Drug: 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 Names:
  • Revlimid
  • CC-5013
  • Rituxan
Active Comparator: B
Subjects aged 65 years and older
Drug: 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 Names:
  • Revlimid
  • CC-5013
  • Rituxan

Detailed Description:

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00628238

Contacts
Contact: Danelle F James, M.D. 858-822-7894 dfjames@ucsd.edu
Contact: Mary Carpenter 858-822-5635 mcarpenter@ucsd.edu

Locations
United States, California
University of California San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Jamie N Gould    858-822-5364    jngould@ucsd.edu   
Contact: Danelle F James    858-822-7894    dfjames@ucsd.edu   
Principal Investigator: Thomas J Kipps, M.D., Ph.D.         
Principal Investigator: Danelle F James, M.D.         
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Evgeny Mikler, P.A.    617-632-4719      
Contact: Clinical Trials Office - Dana-Farber/Harvard Cancer Center    617-582-8480      
Principal Investigator: Jennifer R Brown, M.D.,Ph.D         
United States, New York
Long Island Jewish Medical Center Recruiting
New Hyde Park, New York, United States, 11040
Contact: Nancy Driscoll, RPA-C    516-470-4767    Ndriscol@lij.edu   
Contact    (516)470-4050      
Principal Investigator: Kanti Rai, M.D.         
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Not yet recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Clinical Trials Office - OSU Comprehensive Cancer Center    614-293-4976    osu@emergingmed.com   
Principal Investigator: Michael Grever, M.D.         
Principal Investigator: John Byrd, M.D.         
Sub-Investigator: Thomas Lin, M.D.         
United States, Texas
M. D. Anderson Cancer Center at University of Texas Recruiting
Houston, Texas, United States, 77030-4009
Contact: Susan C Smith    713-745-0553    Susan Smith <scsmith@mdanderson.org>   
Contact: Clinical Trials Office    713-792-3245      
Principal Investigator: William G Wierda, M.D., Ph.D.         
Principal Investigator: Michael J Keating, M.D., B.S.         
Sponsors and Collaborators
Chronic Lymphocytic Leukemia Research Consortium
Celgene Corporation
Investigators
Study Director: Thomas J Kipps, M.D., Ph.D Director of the CLL Research Consortium and University of California San Diego
Principal Investigator: Danelle F James, M.D. CLL Research Consortium and University of California San Diego
  More Information

Additional Information:
Publications:
Responsible Party: Thomas J. Kipps, M.D., Ph.D., Chronic Lymphocytic Leukemia Research Consortium (CRC)
ClinicalTrials.gov Identifier: NCT00628238     History of Changes
Other Study ID Numbers: CRC014, Celgene # RV-CLL-PI-0223
Study First Received: February 26, 2008
Last Updated: September 8, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Chronic Lymphocytic Leukemia Research Consortium:
Chronic Lymphocytic Leukemia Research Consortium
Chronic lymphocytic leukemia
CLL
CLL Research Consortium
CRC
Revlimid
lenalidomide
Rituximab
Rituxan
First-line
therapy
untreated
Frontline

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Thalidomide
Lenalidomide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014