Lenalidomide With or Without Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

CC-5013 Alone or in Combination With Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

RATIONALE: Biological therapies such as lenalidomide use different ways to stimulate the immune system and stop cancer cells from growing. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining lenalidomide with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying the how well giving lenalidomide with or without rituximab works in treating patients with relapsed or refractory chronic lymphocytic leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Biological: rituximab; Drug: lenalidomide

Detailed Description

OBJECTIVES:

Primary

• Determine the best cytostatic response rate (including complete response, partial response, or stable disease) in patients with relapsed or refractory chronic lymphocytic leukemia treated with lenalidomide (CC-5013).

Secondary

• Determine the cytostatic response rate in patients who progress on CC-5013 and are then treated with CC-5013 and rituximab.
• Determine the safety of these regimens in these patients.
• Determine time to progression in patients treated with these regimens.

OUTLINE: This is an open-label, non-randomized, pilot study.

Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) receive 2 additional courses beyond CR.

Patients with disease progression receive oral CC-5013 once daily on days 1-21 and rituximab IV on days 1, 8, and 15 during the first treatment course and on days 1 and 15 of all subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of further disease progression. Patients who achieve CR receive 2 additional courses beyond CR.

Patients are followed at 1 month and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study within 1.5 years.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) by flow cytometry

  • Relapsed or refractory disease

• Measurable disease, defined by 1 of the following criteria:

  • Absolute lymphocyte count ≥ 5,000/mm^3
  • Measurable lymphadenopathy or organomegaly
• Received ≥ 1 prior therapy for CLL

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 30,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if hepatic metastases are present)

Renal

• Creatinine ≤ 1.5 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method (including barrier) contraception during and for 3 months after study participation
• No known hypersensitivity to thalidomide
• No erythema nodosum characterized by a desquamating rash after prior thalidomide or similar drug administration
• No known anaphylaxis or immunoglobulin E-mediated hypersensitivity to murine proteins
• No serious medical condition or laboratory abnormality that would preclude study participation
• No psychiatric illness that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior lenalidomide (CC-5013)
• No concurrent thalidomide

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• At least 4 weeks since prior therapy for CLL
• At least 28 days since prior experimental drug or therapy
• No other concurrent anticancer therapies
• No other concurrent investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Lenalidomide; Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity	Biological: rituximab; IV; Drug: lenalidomide; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Single Agent CC-5013 at 6 Months	Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count >1500/μL; platelet count >100,000/μL; untransfused hemoglobin concentration >11.0g/dL; lymphocyte count <4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD.	at 6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Combination Therapy of CC-5013+Rituximab	Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count >1500/μL; platelet count >100,000/μL; untransfused hemoglobin concentration >11.0g/dL; lymphocyte count <4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients who have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD.	5 years
Number of Participants With Adverse Events on Single Agent CC-5013	Number of Participants with Adverse Events on Single Agent CC-5013, Graded According to NCI CTCAE Version 3.0 Please refer to the adverse event reporting for more detail.	1 year
Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab	Number of Participants with Adverse Events on Combination Therapy of CC-5013+Rituximab, Graded According to NCI CTCAE Version 3.0	Up to 30 days from last date of institution of combination therapy of CC-5013+Rituximab.
Time to Progression for Single Agent CC-5013	Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria.	5 years
Time to Progression for the Combination Therapy of CC-5013+Rituximab	Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria.	Every month up to 6 months and every 3 months thereafter up to 5 years

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: Celgene
• Investigators: Principal Investigator: Kelvin Lee, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: November 9, 2004
• First Submitted That Met QC Criteria: November 8, 2004
• First Posted (Estimate): November 9, 2004

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: refractory chronic lymphocytic leukemia
• 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; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Rituximab
• Other Study ID Numbers: CDR0000391767; RPCI-I-18103 (Other Identifier: Roswell Park Cancer Institute); CELGENE-RV-CLL-PI-005 (Other Grant/Funding Number: Celgene)