Lenalidomide in Treating Patients With High-Risk Chronic Lymphocytic Leukemia

Lenalidomide for the Treatment of CLL Patients With High-Risk Disease

This phase II clinical trial is studying how well lenalidomide works in treating patients with high-risk chronic lymphocytic leukemia. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia
• Intervention / Treatment: Other: Diagnostic Laboratory Biomarker Analysis; Drug: Lenalidomide

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the time to progression in patients with high-risk chronic lymphocytic leukemia (CLL) treated with lenalidomide.

SECONDARY OBJECTIVES:

I. To determine the clinical response (complete and partial response) in treatment-naïve patients with high-risk CLL treated with single-agent lenalidomide.

II. To determine the incidence of immune-mediated flare reaction. III. To determine the toxicity profile of single-agent lenalidomide in previously untreated patients with high-risk CLL.

IV. To conduct correlative studies in bone marrow, peripheral blood, and/or lymph nodes of patients treated with lenalidomide.

OUTLINE:

Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (by morphological criteria but have persistent minimal residual disease by molecular criteria) or partial response may continue treatment beyond 8 courses. Patients may undergo bone marrow, peripheral blood, and/or lymph node sample collection at baseline and periodically during study for correlative studies.

After completion of study therapy, patients are followed up every 3 months for a maximum of 5 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Definitive diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria

  • Must have high-risk B-CLL as defined by ≥ one of the following:

    • High-risk cytogenetics (either 17p deletion and/or 11q deletion)
    • Unmutated immunoglobulin heavy chain gene rearrangement
  • Zap-70 and CD38 expression on leukemic cells will not be used as eligibility criteria for enrollment into the clinical trial
• No prior treatment for the management of B-CLL
• Patients must have B-CLL requiring therapy as defined by the IWCLL criteria

• Must have measurable disease meeting one of the following criteria:

  • Absolute lymphocyte count > 5,000/μL
  • Measurable lymphadenopathy or organomegaly

• No tumor lysis syndrome (TLS) by Cairo-Bishop definition

  • Patients with correction of electrolyte abnormalities allowed
• ECOG performance status 0-2
• ANC ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³
• Creatinine clearance ≥ 30 mL/min
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN (≤ 5 times ULN if hepatic metastases are present)

• Uric acid normal

  • Patients with elevated uric acid allowed provided it is corrected with appropriate pharmacologic measures
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must commit to continued abstinence from heterosexual intercourse or use 2 acceptable methods of contraception (1 highly effective method and 1 additional effective method) ≥ 28 days prior to, during, and for ≥ 28 days after discontinuing lenalidomide
• Able to adhere to the study visit schedule and other protocol requirements
• No serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
• No condition, including the presence of laboratory abnormalities, that would place the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• No known hypersensitivity to thalidomide or lenalidomide
• No history of erythema nodosum characterized by a desquamating rash while taking thalidomide or similar drugs
• No history of any other cancer except non-melanoma skin cancer or carcinoma in-situ of the cervix or cancer for which the patient is in complete remission and off therapy for > 3 years
• No cardiac arrest within the past 6 months
• No known history of hepatitis B infection, positive hepatitis B surface antigen, or positive hepatitis C antibody
• No other concurrent anti-cancer agents or treatments
• More than 28 days since any prior experimental drug or therapy
• Aspirin (81 or 325 mg) or warfarin sodium daily as prophylactic anticoagulation required
• No prior lenalidomide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm I; Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (by morphological criteria but have persistent minimal residual disease by molecular criteria) or partial response may continue treatment beyond 8 courses. Patients may undergo bone marrow, peripheral blood, and/or lymph node sample collection at baseline and periodically during study for correlative studies.

Other: Diagnostic Laboratory Biomarker Analysis; Correlative studies; Drug: Lenalidomide; Given orally; Other Names: CC-5013; Revlimid; CC5013; CDC 501

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to progression	From the start of lenalidomide therapy to time of disease progression, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal clinical response (complete and partial response)	Summarized by a sample proportion along with the exact 95% confidence interval. The time-to-progression will be graphically analyzed using standard Kaplan-Meier estimation.	Up to 24 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: January 5, 2011
• First Submitted That Met QC Criteria: January 5, 2011
• First Posted (Estimate): January 6, 2011

Study Record Updates

• Last Update Posted (Estimate): June 4, 2015
• Last Update Submitted That Met QC Criteria: June 3, 2015
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: NCI-2011-02568 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA016056 (U.S. NIH Grant/Contract); CDR0000692070; RPCI # I 174910 (Other Identifier: Roswell Park Cancer Institute); 8254 (Other Identifier: CTEP)