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Safety And Efficacy Of Lenalidomide In Patients With Relapsed Or Refractory Aggressive Non-Hodgkin's Lymphoma (NHL)

This study has been completed.
Sponsor:
Collaborator:
Prologue Research International
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00179660
First received: September 13, 2005
Last updated: June 25, 2013
Last verified: June 2013
  Purpose

To determine the activity of lenalidomide in relapsed or refractory aggressive NHL.


Condition Intervention Phase
Non-Hodgkins Lymphoma
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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 Subjects With Relapsed Or Refractory Aggressive 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 3.7 months, with a maximum of 32.5 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 3.7 months, with a maximum of 32.5 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.

  • Duration of Response [ Time Frame: From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 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.

  • Duration of Tumor Control [ Time Frame: From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months. ] [ Designated as safety issue: No ]
    The duration of tumor control was calculated as the time from the first response assessment demonstrating at least stable disease to the first documentation of progressive disease or death due to NHL. 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 [ Time Frame: From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 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 15.2 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: 50
Study Start Date: August 2005
Study Completion Date: June 2008
Primary Completion Date: June 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
Capsules for oral administration.
Other Names:
  • CC-5013
  • Revlimid®

  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
  5. Aggressive lymphoma, the following histologies are acceptable: Follicular center lymphoma, grade 3, Diffuse large cell, Mantle cell, Transformed
  6. Relapsed or refractory to previous therapy for lymphoma. Patients 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. Patients 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. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug.

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 aspartate transaminase (AST) or alanine transaminase (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 patients with central nervous system (CNS) disease with the exception of those patients 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 (CT) scan or magnetic resonance imaging (MRI), for at least 6 months.
  4. Prior history of malignancies other than non-Hodgkin's lymphoma (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 > or equal to grade 3 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) allergic reaction/hypersensitivity to thalidomide
  9. Prior > or equal to grade 3 NCI CTCAE 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
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: NCT00179660

Locations
United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259
United States, California
Pacific Coast Hematology/Oncology Medical Group, Onc.
Fountain Valley, California, United States, 92708
UC David Cancer Center
Sacramento, California, United States, 95817
United States, Florida
Sylvester Cancer CenterUniversity Of Miami
Miami, Florida, United States, 33136
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, Wisconsin
Gunderson Clinic, Ltd
La Crosse, Wisconsin, United States, 54601
Sponsors and Collaborators
Celgene Corporation
Prologue Research International
  More Information

Publications:
Peter H. Wiernik, Izidore S. Lossos, Joseph M. Tuscano, Glen Justice, Julie M. Vose, Craig E. Cole, Wendy Lam, Kyle McBride, Kenton Wride, Dennis Pietronigro, Kenichi Takeshita, Annette Ervin-Haynes, Jerome B. Zeldis, and Thomas M. Habermann. Lenalidomide Monotherapy in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma. Journal of Clinical Oncology 26:4952-4957, 2008.

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00179660     History of Changes
Other Study ID Numbers: CC-5013-NHL-002
Study First Received: September 13, 2005
Results First Received: June 25, 2013
Last Updated: June 25, 2013
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on November 19, 2014