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

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

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

Study Overview

• Status: Completed
• Conditions: Non-Hodgkins Lymphoma
• Intervention / Treatment: Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • California
    • Fountain Valley, California, United States, 92708
      • Pacific Coast Hematology/Oncology Medical Group, Onc.
    • Sacramento, California, United States, 95817
      • UC David Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Cancer CenterUniversity Of Miami
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6805
      • University of Nebraska
  • New York
    • Bronx, New York, United States, 10466
      • New York Medical Center, MBCCOP
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gunderson Clinic, Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Response	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.	From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Tumor Control	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.	From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.
Duration of Response	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.	From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.
Duration of Tumor Control	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.	From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.
Progression-free Survival	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.	From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.
Number of Participants With Adverse Events (AEs)	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.	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.

Collaborators and Investigators

• Sponsor: Celgene Corporation
• Collaborators: Prologue Research International

Publications and helpful links

General Publications

• Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. doi: 10.1200/JCO.2007.15.3429. Epub 2008 Jul 7.

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (ACTUAL): June 1, 2008
• Study Completion (ACTUAL): June 1, 2008

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (ESTIMATE): September 16, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): January 21, 2016
• Last Update Submitted That Met QC Criteria: December 17, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: NHL; Revlimid; Non-Hodgkins Lymphoma; CC5013; celgene; cc-5013
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: CC-5013-NHL-002