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Study of Lenalidomide to Evaluate Safety and Efficacy in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT00963105
Recruitment Status : Completed
First Posted : August 21, 2009
Results First Posted : October 2, 2018
Last Update Posted : October 2, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:
The purpose of this study is to determine the safety and effectiveness of different dose regimens of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Chronic Lymphocytic Leukemia Drug: lenalidomide Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Multi-Center, Randomized, Double-Blinded, Parallel Group Study of the Safety and Efficacy of Different Lenalidomide (REVLIMID®) Dose Regimens in Subjects With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia
Actual Study Start Date : October 19, 2009
Actual Primary Completion Date : September 5, 2017
Actual Study Completion Date : September 5, 2017


Arm Intervention/treatment
Experimental: Lenalidomide 5 mg

Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.

Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug

Drug: lenalidomide

Depending on the starting dose, subjects will be allocated in a double-blind fashion to three different regimens and will escalate every 28 days, based on individual subject tolerability, as follows:

  • Treatment Arm 1: 5 mg →10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 2: 10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 3: 15 mg →20 mg →25 mg/daily Subjects will continue treatment until disease progression or unacceptable toxicity

Experimental: Lenalidomide 10 mg

Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.

Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug

Drug: lenalidomide

Depending on the starting dose, subjects will be allocated in a double-blind fashion to three different regimens and will escalate every 28 days, based on individual subject tolerability, as follows:

  • Treatment Arm 1: 5 mg →10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 2: 10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 3: 15 mg →20 mg →25 mg/daily Subjects will continue treatment until disease progression or unacceptable toxicity

Experimental: Lenalidomide 15 mg

Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability.

Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug

Drug: lenalidomide

Depending on the starting dose, subjects will be allocated in a double-blind fashion to three different regimens and will escalate every 28 days, based on individual subject tolerability, as follows:

  • Treatment Arm 1: 5 mg →10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 2: 10 mg →15 mg →20 mg →25 mg/daily
  • Treatment Arm 3: 15 mg →20 mg →25 mg/daily Subjects will continue treatment until disease progression or unacceptable toxicity




Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events [ Time Frame: From first dose of study drug to 30 days after the last dose; the maximum duration of treatment was 251, 265, and 267 weeks in the 5 mg, 10 mg, and 15 mg treatment groups respectively. ]
    Adverse events (AEs) were graded for severity by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 with the exceptions of hematologic toxicities and tumor lysis syndrome, according to the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening or disabling AE Grade 5 = Death The investigator determined the relationship of each AE to study drug based on the timing of the AE and whether other medications, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the observed event.


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months. ]
    Overall response rate was defined as the percentage of participants with a complete response (CR), CR with incomplete bone marrow recovery (CRi) or partial response (PR) during the treatment period. Tumor response was assessed by the investigator according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines for the diagnosis and treatment of CLL, based on laboratory, physical exam, assessment of constitutional symptoms and if appropriate computed tomography (CT) scan findings (to confirm PR or CR/CRi). For confirmed PR or CR/CRi, response had to be maintained for ≥ 8 weeks.

  2. Kaplan-Meier Estimate of Duration of Response [ Time Frame: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months. ]
    Duration of response (DOR) was defined as the time from the first visit where PR, CRi, or CR was documented to progressive disease (PD). Duration of response was censored at the last date that the participant was known to be progression-free for participants who had not progressed at the time of analysis or who withdrew consent or were lost to follow-up prior to documentation of progression.

  3. Time to Response [ Time Frame: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months. ]
    Time to response (TTR) was calculated as the time from randomization to the first documented date of response (PR, CRi or CR) based on iwCLL guidelines for participants with an objective response during the treatment period.

  4. Kaplan-Meier Estimate of Time to Progression [ Time Frame: From randomization until the end of the study; maximum time on study was 91 months. ]
    Time to progression (TTP) was defined as the time from randomization to the first documented progression. For participants who did not progress during the study, TTP was censored at the last adequate response assessment showing evidence of no disease progression.

  5. Kaplan-Meier Estimate of Event-Free Survival [ Time Frame: From randomization until the end of the study; maximum time on study was 91 months. ]
    Event-free survival (EFS) is the interval between the start of treatment to the first sign of disease progression, or treatment for relapse or death (whichever occurred first). If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.

  6. Kaplan-Meier Estimate of Progression Free Survival [ Time Frame: From randomization until the end of the study; maximum time on study was 91 months. ]
    Progression-free survival (PFS) was calculated as the time from randomization to the first documented progression or death due to any cause during or after the treatment period, whichever occurred first. The progression date was assigned to the earliest time when any progression is observed without prior missing assessments. If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.

  7. Kaplan-Meier Estimate of Overall Survival [ Time Frame: From randomization until the end of the study; maximum time on study was 91 months. ]
    Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who had withdrawn consent or were lost to follow-up before death was documented.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years at the time of signing the informed consent form
  • Must be able to adhere to the study visit schedule and other protocol requirements
  • Must have a documented diagnosis of B-cell CLL
  • Must be relapsed or refractory to at least 1 regimen for treatment of CLL. At least one of the prior treatments must have included a purine analog-based or bendamustine-based regimen
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • Active infections requiring systemic antibiotics
  • Systemic treatment for B-cell CLL within 28 days of initiation of lenalidomide treatment
  • Alemtuzumab therapy within 120 days of initiating lenalidomide treatment
  • Prior therapy with lenalidomide
  • History of grade 4 rash due to prior thalidomide treatment
  • Planned autologous or allogeneic bone marrow transplantation
  • Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging.
  • Uncontrolled hyperthyroidism or hypothyroidism
  • Venous thromboembolism within 12 months
  • ≥ Grade 2 neuropathy
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia]
  • Participation in any clinical study or having taken any investigational therapy within 28 days prior to initiating lenalidomide therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00963105


  Show 52 Study Locations
Sponsors and Collaborators
Celgene
Investigators
Study Director: Jeffery Jones, M.D., MPH Celgene Corporation
  Study Documents (Full-Text)

Documents provided by Celgene:
Study Protocol  [PDF] April 15, 2015
Statistical Analysis Plan  [PDF] November 1, 2012


Publications:
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT00963105     History of Changes
Other Study ID Numbers: CC-5013-CLL-009
2009-009836-54 ( EudraCT Number )
First Posted: August 21, 2009    Key Record Dates
Results First Posted: October 2, 2018
Last Update Posted: October 2, 2018
Last Verified: September 2018

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