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

NCT00628238 | Unknown Phase 2 DMC

• 2 other identifiers: CRC014Celgene # RV-CLL-PI-0223
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Chronic Lymphocytic Leukemia; CLL; Untreated; Front-line; First-Line; Initial Therapy

Keywords

Chronic Lymphocytic Leukemia Research Consortium; Chronic lymphocytic leukemia; CLL; CLL Research Consortium; CRC; Revlimid; lenalidomide; Rituximab; Rituxan; First-line; therapy; untreated; Frontline

Outcome Measures

Primary Outcomes (1)

• 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.

  clinical response assessment after 3 cycles of therapy and 3 months following completion of all therapy for NCI-CLL working group response assessment

Secondary Outcomes (5)

• Safety - type, frequency, severity, and relationship of adverse events to study treatment

  Throughout the study period

• Time To Progression

  Following therapy until disease progression

• Evaluate response to lenalidomide in relationship to molecular and genetic prognostic features in CLL; including ZAP-70 status, IgVH gene mutational status, and FISH.

  Following final response assessment

• Compare the efficacy and tolerability of the combination of Revlimid and rituximab for patients younger than 65 years, and for those 65 and older. •

  following final response assessment

• Evaluate change in hematological parameters including neutropenia, anemia, and thrombocytopenia following treatment with the combination of Revlimid and rituximab.

  Following final response assessment

Study Arms (2)

A

ACTIVE COMPARATOR

Subjects younger than 65 years old.

Drug: Lenalidomide and Rituximab

B

ACTIVE COMPARATOR

Subjects aged 65 years and older

Drug: Lenalidomide and Rituximab

Interventions

Lenalidomide and Rituximab DRUG

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.

Also known as: Revlimid, CC-5013, Rituxan

A

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of chronic lymphocytic leukemia with no history of previous treatments with monoclonal antibodies or chemotherapy.
• Subjects must have an indication for treatment as defined by the NCI Working Group Guidelines
• Understand and voluntarily sign an informed consent form.
• Age ≥18 years at the time of signing the informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• ECOG performance status of ≤ 2 at study entry (see Appendix A).
• 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
• 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.
• 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

You may not qualify if:

• Previous treatment for CLL with chemotherapy or monoclonal antibodies
• Known Hepatitis B Ag positive, Hepatitis C positive patients
• Known HIV positive patients
• Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
• Inability to provide informed consent.
• Concurrent malignancy (excluding basal and squamous cell skin cancers).
• Active fungal, bacterial, and/or viral infection.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast-feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
• 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.
• Use of any other experimental drug or therapy within 28 days of baseline.
• Known hypersensitivity to thalidomide.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Any prior use of lenalidomide.
• Concurrent use of other anti-cancer agents or treatments.

Sponsors & Collaborators

• Chronic Lymphocytic Leukemia Research Consortium: lead
• Celgene Corporation: collaborator

Study Sites (5)

University of California San Diego

La Jolla, California, 92093, United States

RECRUITING

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

RECRUITING

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University

Columbus, Ohio, 43210-1240, United States

NOT YET RECRUITING

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 17088571 BACKGROUND

• 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.

  PMID: 16750498 BACKGROUND

• 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.

  PMID: 18334676 BACKGROUND

Related Links

• Website for the CLL Research Consortium
• Moore's UCSD Cancer Center

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Thomas J Kipps, M.D., Ph.D

  Director of the CLL Research Consortium and University of California San Diego

  STUDY DIRECTOR

• Danelle F James, M.D.

  CLL Research Consortium and University of California San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danelle F James, M.D.

CONTACT

858-822-7894; dfjames@ucsd.edu

Mary Carpenter

CONTACT

858-822-5635; mcarpenter@ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Expanded Access: Yes

Study Record Dates

• First Submitted: February 26, 2008
• First Posted: March 5, 2008
• Study Start: February 1, 2008
• Primary Completion: February 1, 2011
• Study Completion: July 1, 2011
• Last Updated: September 10, 2010

Record last verified: 2010-09

Locations

US (5)