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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Lenalidomide

About this trial

This is an interventional treatment trial for Non-Hodgkins Lymphoma focused on measuring celgene, cc-5013, CC5013, NHL, Non-Hodgkins Lymphoma, Revlimid

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Understand and voluntarily sign an informed consent form. Age greater than or equal to 18 years at the time of signing the informed consent form Able to adhere to the study visit schedule and other protocol requirements Biopsy-proven non-Hodgkin's lymphoma Aggressive lymphoma, the following histologies are acceptable: Follicular center lymphoma, grade 3, Diffuse large cell, Mantle cell, Transformed 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. Patients must have measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2. 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: Any of the following laboratory abnormalities: Absolute neutrophil count (ANC) <1,500 cells/mm^3 (1.5 x 10^9/L) Platelet count <100,000/mm^3 (100 x 10^9/L) Serum creatinine >2.5 mg/dL (221 mmol/L) Serum aspartate transaminase (AST) or alanine transaminase (ALT) >5.0 x upper limit of normal (ULN) Serum total bilirubin >2.0 mg/dL (34 mmol/L) 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 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. 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 Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form Known positive for human immunodeficiency virus (HIV) Pregnant or lactating females Prior > or equal to grade 3 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) allergic reaction/hypersensitivity to thalidomide Prior > or equal to grade 3 NCI CTCAE rash or any desquamating (blistering) rash while taking thalidomide Prior use of lenalidomide Use of any standard or experimental anti-cancer drug therapy within 28 days of day 1 of study drug therapy Known active Hepatitis C

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT00179660

First Posted

September 13, 2005

Last Updated

December 17, 2015

Sponsor

Celgene Corporation

Collaborators

Prologue Research International

1. Study Identification

Unique Protocol Identification Number

NCT00179660

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

August 2005 (undefined)

Primary Completion Date

June 2008 (Actual)

Study Completion Date

June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Celgene Corporation

Collaborators

Prologue Research International

4. Oversight

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Hodgkins Lymphoma

Keywords

celgene, cc-5013, CC5013, NHL, Non-Hodgkins Lymphoma, Revlimid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lenalidomide

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Lenalidomide

Other Intervention Name(s)

CC-5013, Revlimid®

Intervention Description

Capsules for oral administration.

Primary Outcome Measure Information:

Title

Percentage of Participants With Response

Description

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.

Time Frame

From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Secondary Outcome Measure Information:

Title

Percentage of Participants With Tumor Control

Description

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.

Time Frame

From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Title

Duration of Response

Description

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.

Time Frame

From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Title

Duration of Tumor Control

Description

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.

Time Frame

From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Title

Progression-free Survival

Description

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.

Time Frame

From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Title

Number of Participants With Adverse Events (AEs)

Description

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.

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Understand and voluntarily sign an informed consent form. Age greater than or equal to 18 years at the time of signing the informed consent form Able to adhere to the study visit schedule and other protocol requirements Biopsy-proven non-Hodgkin's lymphoma Aggressive lymphoma, the following histologies are acceptable: Follicular center lymphoma, grade 3, Diffuse large cell, Mantle cell, Transformed 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. Patients must have measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2. 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: Any of the following laboratory abnormalities: Absolute neutrophil count (ANC) <1,500 cells/mm^3 (1.5 x 10^9/L) Platelet count <100,000/mm^3 (100 x 10^9/L) Serum creatinine >2.5 mg/dL (221 mmol/L) Serum aspartate transaminase (AST) or alanine transaminase (ALT) >5.0 x upper limit of normal (ULN) Serum total bilirubin >2.0 mg/dL (34 mmol/L) 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 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. 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 Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form Known positive for human immunodeficiency virus (HIV) Pregnant or lactating females Prior > or equal to grade 3 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) allergic reaction/hypersensitivity to thalidomide Prior > or equal to grade 3 NCI CTCAE rash or any desquamating (blistering) rash while taking thalidomide Prior use of lenalidomide Use of any standard or experimental anti-cancer drug therapy within 28 days of day 1 of study drug therapy Known active Hepatitis C

Facility Information:

Facility Name

Mayo Clinic Scottsdale

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259

Country

United States

Facility Name

Pacific Coast Hematology/Oncology Medical Group, Onc.

City

Fountain Valley

State/Province

California

ZIP/Postal Code

92708

Country

United States

Facility Name

UC David Cancer Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

Facility Name

Sylvester Cancer CenterUniversity Of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

University of Nebraska

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198-6805

Country

United States

Facility Name

New York Medical Center, MBCCOP

City

Bronx

State/Province

New York

ZIP/Postal Code

10466

Country

United States

Facility Name

Gunderson Clinic, Ltd

City

La Crosse

State/Province

Wisconsin

ZIP/Postal Code

54601

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

18606983

Citation

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.

Results Reference

result

Non-Hodgkins Lymphoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial