Study of Lenalidomide in Previously Untreated, Symptomatic Chronic Lymphocytic Leukemia (CLL) (Rev-CLL)

This study has been terminated.
(Seven years of follow-up & final analysis done in Dec 2012.)
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00751296
First received: September 10, 2008
Last updated: May 12, 2016
Last verified: May 2016
  Purpose

This study will assess the

  • efficacy (response rate) of oral lenalidomide in the treatment of patients with symptomatic, previously untreated, chronic lymphocytic leukemia (CLL),
  • toxicity of lenalidomide in patients with CLL as well as time to progression, stable disease duration and, if responses are observed, response duration.

Condition Intervention Phase
Chronic Lymphocytic Leukaemia
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Lenalidomide in Previously Untreated, Symptomatic Chronic Lymphocytic Leukemia (CLL)

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • To Assess the Efficacy (Response Rate) of Oral Lenalidomide in the Treatment of Patients With Symptomatic, Previously Untreated, Chronic Lymphocytic Leukemia (CLL) [ Time Frame: Patients will be treated with lenalidomide until disease progression or 2 cycles past CR (no maximum of cycles). Participants were followed upto 53.2 months for the final data analysis. ] [ Designated as safety issue: No ]

    The primary endpoint was objective response to lenalidomide (Complete response +Partial response) evaluated as per the revised 1996 National Cancer Institute Working Group Guidelines.

    Complete response: absence of lymphadenopathy and organomegaly by physical exam and radiology, absence of constitutional symptoms, normal CBC. Bone marrow to be done 2 months after the above criteria are met, must be normocellular, with <30% lymphocytes.

    Partial Response: ≥ 50% decrease in the peripheral blood lymphocytes from pre-treatment value, ≥ 50% reduction in lymphadenopathy and organomegaly by physical exam or on CT scan. one or more of the following: neutrophils ≥ 1.5 x109/L, platelets > 100 x109/L or 50% improvement over baseline, hemoglobin > 110 g/L or 50% improvement over baseline (without transfusion).



Secondary Outcome Measures:
  • Percentage of Participants With Progression-free Survival (PFS) and Overall Survival (OS). [ Time Frame: Patients will be treated with lenalidomide until disease progression or 2 cycles past CR (no maximum of cycles). Participants were followed upto 53.2 months for the final data analysis. ] [ Designated as safety issue: Yes ]
    Assess the time to disease progression and overall survival. (Progressive disease is defined as at least one of the following: more than or equal to 50% increase in the sum of the products of the greatest diameters of at least 2 lymph nodes on 2 consecutive determinations 2 weeks apart (at least one node must be ≥ 2 cm) or new palpable lymph nodes, more than or equal to 50% increase in the size of the liver and/or spleen as determined by measurement below the costal margin or appearance of palpable hepatomegaly or splenomegaly not previously present, more than or equal to 50% increase in the absolute number of circulating lymphocytes to at least 5.0 x109/L, OR transformation to a more aggressive histology (e.g. Richter's syndrome or prolymphocytic leukemia with >55% prolymphocytes)).


Enrollment: 27
Study Start Date: August 2006
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidiomide
Lenalidomide target dose of 10 mg PO OD X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28-day cycle.
Drug: Lenalidomide
Subjects will receive lenalidomide, starting at 2.5 mg daily x 3 weeks (days 1-21) and escalating up to a target dose of 10 mg daily X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28 day cycle.Patients will be treated with lenalidomide until disease progression or 2 cycles past CR. (no maximum of cycles).
Other Name: REVLIMID®

Detailed Description:
This is a phase II, nonrandomized, single institution study in symptomatic, previously untreated CLL patients. Subjects will receive the study drug, lenalidomide, starting at 2.5 mg daily x 3 weeks (days 1-21) and escalating up to a target dose of 10 mg daily X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28 day cycle. Although a maximal dose of 10 mg daily (days 1-21) will be targeted, if a patient is felt by the investigator to be benefiting from doses less than the target dose (i.e. 2.5 mg or 5 mg daily), the investigator may at his discretion choose to hold the patient at that dose without further escalation. For those patients who have progressive disease after cycle 3, further dose escalations as assessed by response and toxicity at the end of each escalated dose cycle to a maximum of 25 mg (days 1-21) will be allowed. Patients will be treated with lenalidomide until disease progression or 2 cycles past CR. (no maximum of cycles).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • A confirmed diagnosis of B-cell CLL by NCI Working Group criteria
  • No prior systemic therapy for CLL. Steroid therapy alone for autoimmune cytopenias (anemia or thrombocytopenia) is NOT considered a prior systemic therapy.
  • Radiation: Patients may have received prior radiation therapy restricted to ≤ 25% of functioning bone marrow. Patients must be ≥ 4 weeks since last treatment with radiation therapy.
  • Surgery: previous surgery is permissible. Patient must be ≥ 4 weeks since any major surgery.
  • Patients must have symptomatic disease requiring therapy. One or more of the following must be present to be eligible:

    • Symptomatic lymphadenopathy
    • Hepatomegaly and/or splenomegaly
    • Anemia (Hb <110 g/L)
    • Thrombocytopenia (platelets <100)
    • Fatigue, weight loss, night sweats, fever (without infection) or other constitutional symptoms felt to require treatment as per treating physician discretion
    • Persistent rise in lymphocyte count with doubling time of < 12 months
  • ECOG performance status of ≤ 2 at study entry.
  • Laboratory Requirements: (must be done within 7 days prior to first study drug dose)

Hematology: Absolute granulocytes (AGC) ≥ 1.0 x 109/L Platelets ≥ 50 x 109/L Chemistry: Serum creatinine ≤ 1.5 x UNL Bilirubin ≤ 1.5 x UNL AST (or ALT if AST ≤ 2.5 x UNL not available)

  • Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to therapy and repeated within 24 hours of starting study drug and must either commit to continued abstinence from heterosexual sexual intercourse or begin TWO acceptable methods of birth control, one highly effective methods and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. In addition, sexually active WCBP must agree to ongoing pregnancy testing. Men must agree not to father a child and agrees to use a condom if his partner is of child bearing potential.
  • Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast

Exclusion Criteria:

  • Patients who fulfill any of the following criteria are not eligible for admission to the study:
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Pregnant or lactating 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.
  • Patients previously or currently receiving treatment with other anti-cancer therapy for CLL
  • Lymphoproliferative disease other than CLL (includes patients with prolymphocytic leukemia, mantle cell lymphoma, and those who have transformed to a more aggressive lymphoma, or Richter's syndrome).
  • 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.
  • Known positive for HIV or infectious hepatitis, type A, B or C.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00751296

Locations
Canada, Ontario
University Health Network - Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
Celgene
Investigators
Principal Investigator: Christine I Chen, MD University Health Network, Toronto
  More Information

Additional Information:
Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00751296     History of Changes
Other Study ID Numbers: Rev-06-0099  RV-CLL-PI-0099 
Study First Received: September 10, 2008
Results First Received: December 29, 2015
Last Updated: May 12, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Lenalidomide
immunomodulatory drug (IMiD®)
Thalidomide analogues

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

ClinicalTrials.gov processed this record on August 25, 2016