Lenalidomide (Revlimid®, CC-5013) in Subjects With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Prologue Research International
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00179673
First received: September 10, 2005
Last updated: November 6, 2013
Last verified: November 2013
  Purpose

Participants who qualify will receive lenalidomide daily on days 1-21 of every 28 day cycle. Treatment will continue for up to 52 weeks or until disease progression; participants who achieve a complete response (CR) will receive an additional 2 cycles of treatment prior to discontinuation. Participants will be followed for progression free survival following discontinuation from the treatment phase


Condition Intervention Phase
Non-Hodgkins Lymphoma
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 II, Multicenter, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of Single-Agent Lenalidomide (Revlimid®, CC-5013) in Participants With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Percentage of Participants With Response [ Time Frame: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months ] [ Designated as safety issue: No ]

    Response was defined as participants with a complete response (CR), unconfirmed complete response (Cru) or partial response (PR), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities.

    Cru: Criteria for CR above but with 1 or more of the following:

    • A residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD)
    • Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia).

    PR: ≥ 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD.



Secondary Outcome Measures:
  • Percentage of Participants With Tumor Control [ Time Frame: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months ] [ Designated as safety issue: No ]

    Tumor control was defined as participants with a complete response, unconfirmed complete response, partial response or stable disease (SD), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator.

    SD was defined as a response less than a PR (see above) but not Progressive Disease (PD).

    PD was defined as

    • ≥ 50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or non-responders.
    • Appearance of any new lesion during or at the end of therapy.

  • The Duration of Response [ Time Frame: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months ] [ Designated as safety issue: No ]
    The duration of response was calculated as the first response assessment demonstrating evidence of at least a partial response to the first documentation of progressive disease (as determined by computed tomography scan) or death due to NHL, whichever occurred first. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate.

  • Progression Free Survival (PFS) [ Time Frame: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months ] [ Designated as safety issue: No ]
    Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first. Participants who withdrew for any reason or received another NHL therapy including stem cell transplantation without documented progressive disease were censored on the date of their last adequate response assessment indicating no progression (or last adequate assessment prior to receiving other NHL therapy). Participants who were still active without progressive disease at the time of the data cut-off date were censored on the date of their last adequate response assessment.

  • Number of Participants With Adverse Events (AEs) [ Time Frame: From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 13.8 months. ] [ Designated as safety issue: Yes ]

    The Investigator determined the relationship between the administration of study drug and the occurrence of an AE as suspected if the temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other drugs, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event.

    The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria and the following scale:

    • Grade 1 = Mild
    • Grade 2 = Moderate
    • Grade 3 = Severe
    • Grade 4 = Life threatening
    • Grade 5 = Death

    A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event.



Enrollment: 43
Study Start Date: August 2005
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide
Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Drug: Lenalidomide
Lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed
Other Name: CC-5013; Revlimid®

Detailed Description:

Participants who qualified for enrollment into the study entered the treatment phase and received single-agent lenalidomide 25 mg once daily on Days 1 to 21 of every 28-day cycle. The treatment phase began on Day 1 of Cycle 1. Study visits were scheduled to occur every 28 days to coincide with the beginning of a new cycle. The start date of a new cycle was delayed if adverse events (AEs) occurred, in which case the visit date for the start of the following cycle was scheduled 28 days after the actual start date of the delayed cycle. Efficacy and safety assessments, including complete blood counts (CBCs) were performed at least every 2 weeks during Cycles 1 to 4 of the treatment phase. Participants continued in the treatment phase of the study for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Understand and voluntarily sign an informed consent form.
  2. Age greater than or equal to 18 years at the time of signing the informed consent form
  3. Able to adhere to the study visit schedule and other protocol requirements
  4. Biopsy-proven non-Hodgkin's lymphoma (NHL)
  5. Indolent lymphoma the following histologies are acceptable:

    1. Follicular center lymphoma, grades 1, 2,
    2. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type,
    3. Nodal marginal zone B-cell lymphoma
    4. Splenic marginal zone B-cell lymphoma,
    5. Small lymphocytic lymphoma,
    6. Lymphoplasmacytoid lymphoma
  6. Relapsed or refractory to previous therapy for lymphoma. Participants must have received at least one prior treatment regimen such as radiation, immunotherapy, chemotherapy, OR radioimmunotherapy, and be ineligible or unwilling to undergo an autologous stem cell transplant. There is no limit on the number of prior therapies
  7. Participants must have measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter
  8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
  9. Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception or to practice complete abstinence from heterosexual intercourse during the following periods 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed.

Exclusion Criteria:

  1. Any of the following laboratory abnormalities

    1. Absolute neutrophil count (ANC) <1,500 cells/mm^3 (1.5 x 10^9/L)
    2. Platelet count <100,000/mm^3 (100 x 10^9/L)
    3. Serum creatinine >2.5 mg/dL (221 mmol/L)
    4. Serum glutamic-oxaloacetic transaminase/ aspartate aminotransferase (SGOT/AST) or serum glutamic:pyruvic transaminase/alanine aminotransferase (SGPT/ALT) >5.0 x upper limit of normal (ULN)
    5. Serum total bilirubin >2.0 mg/dL (34 mmol/L)
  2. 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.
  3. All participants with Central Nervous System (CNS) disease with the exception of those subjects whose CNS disease has been treated with chemotherapy, radiotherapy or surgery and remains asymptomatic, with no active CNS disease, as shown by lumbar puncture, Computed Tomography or Magnetic resonance imaging (CT scan or MRI), for at least 6 months.
  4. Prior history of malignancies other than NHL (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for > or equal to 1 year.
  5. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  6. Known positive for Human Immunodeficiency Virus (HIV).
  7. Pregnant or lactating females.
  8. Prior ≥ grade 3 (National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI CTCAE]) allergic reaction/hypersensitivity to thalidomide.
  9. Prior ≥ grade 3 rash or any desquamating (blistering) rash while taking thalidomide.
  10. Prior use of lenalidomide.
  11. Use of any standard or experimental anti-cancer drug therapy within 28 days of day 1 of study drug therapy.
  12. Known active Hepatitis C.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00179673

Locations
United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259
United States, California
Alta Bates Cancer Center
Berkeley, California, United States, 94704
Pacific Coast Hematology/Oncology Medical Group, Onc.
Fountain Valley, California, United States, 92708
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Massachusetts
Harvard University
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Nebraska
University of Nebraska
Omaha, Nebraska, United States, 68198-6805
United States, New York
New York Medical Center, MBCCOP
Bronx, New York, United States, 10466
United States, Ohio
Signal Point Hematology/Oncology
Middletown, Ohio, United States, 45042
United States, Washington
Swedish Cancer Institute
Seattle, Washington, United States, 98104
United States, Wisconsin
Gunderson Clinic, Ltd.
La Crosse, Wisconsin, United States, 54601
Canada, British Columbia
BC Community Oncology Trialist
Burnaby, British Columbia, Canada, V5H 4K7
BC Community Oncology
North Vancouver, British Columbia, Canada, V7L 2P9
Canada, Ontario
London Regional Cancer Program
London, Ontario, Canada, N6A 5W9
Canada, Saskatchewan
University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Sponsors and Collaborators
Celgene Corporation
Prologue Research International
Investigators
Study Director: Robert Knight, MD Celgene Corporation
  More Information

Publications:
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00179673     History of Changes
Other Study ID Numbers: CC-5013-NHL-001
Study First Received: September 10, 2005
Results First Received: August 9, 2013
Last Updated: November 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
NHL
CC5013
Non-Hodgkins Lymphoma
revlimid
cc-5013
celgene

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014