Study of Lenalidomide to Evaluate Safety and Effectiveness in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01197560
First received: July 29, 2010
Last updated: July 31, 2014
Last verified: July 2014
Results First Received: July 31, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Diffuse Large B-cell Lymphoma
Interventions: Drug: Lenalidomide
Drug: Gemcitabine
Drug: Oxaliplatin
Drug: Rituximab
Drug: Etoposide

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Lenalidomide Lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may be increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Investigator's Choice (Control Arm)

Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal.

Participants with documented progressive disease were permitted to crossover to receive lenalidomide at the participant's request and at the investigators' discretion at the same doses mentioned.


Participant Flow:   Overall Study
    Lenalidomide     Investigator's Choice (Control Arm)  
STARTED     54 [1]   57 [1]
Received ≥ One Dose Study Drug     54     55  
Lenalidomide Crossover     0     29  
Discontinued Treatment After ≥ 6 Cycles     7     3  
COMPLETED     8 [2]   4 [3]
NOT COMPLETED     46     53  
Adverse Event                 4                 8  
Death                 1                 5  
Withdrawal by Subject                 1                 1  
Disease progression                 39                 35  
Proceeded to transplant                 1                 1  
Elected to discontinue before cycle end                 0                 2  
Missing                 0                 1  
[1] This is the intent to treat population
[2] Completed equals participants ongoing on treatment at the time of the data cut-off of 04 July 2013
[3] Completed = those completed and ongoing on treatment at the time of the data cut-off of 04 July 2013



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Modified Intent to Treat (mITT) = all study participants randomized with a Diffuse Large B-Cell Lymphoma (DLBCL) diagnosis and Germinal center B-cell (GCB)/non-Germinal center B (non-GCB) subtype confirmed by Central Pathology, and who received at least one dose of study drug (lenalidomide or Investigator’s choice). Nine participants were excluded.

Reporting Groups
  Description
Lenalidomide Lenalidomide 25 mg orally once daily for 21 days in each 28-day cycle until progressive disease. For participants with creatinine clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10mg once daily for 21 days for 2 cycles. After Cycle 2 the dose may be increased to a maximum of 15 mg lenalidomide once daily for 21 days in each 28-day cycle. Treatment was continued until disease progression, unacceptable toxicity, or voluntary withdrawal.
Investigator's Choice

Participants received a single agent reference therapy (either gemcitabine, oxaliplatin, rituximab or etoposide) based on published data for up to 6 cycles or until disease progression, unacceptable toxicity or withdrawal.

Gemcitabine 1,250 mg/m^2 Intravenous (IV) days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m^2 IV days 1 and 15 in each 28- day cycle for 6 Cycles

Oxaliplatin 100 mg/m^2 IV day 1 in each 21-day cycle for 6 Cycles

Rituximab is 375 mg/m^2 IV days 1, 8, 15, 22 during Cycle 1, and if stable disease at Week 12, also on Day 1 of Cycles 4, 6, 8, and 10 (CD20+ patients only)

Etoposide doses:

100 mg/m^2 IV days 1-5 in each 28-day cycle for 6 Cycles, or 100 mg/m^2 IV days 1-3 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-21 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-14 in each 28-day cycle for 6 Cycles, or 50 mg/m^2 oral days 1-10 in each 28-day cycle for 6 Cycles

Total Total of all reporting groups

Baseline Measures
    Lenalidomide     Investigator's Choice     Total  
Number of Participants  
[units: participants]
  51     51     102  
Age  
[units: years]
Mean ± Standard Deviation
  64.7  ± 13.43     62.8  ± 13.94     63.75  ± 13.69  
Gender  
[units: participants]
     
Female     21     20     41  
Male     30     31     61  
Race/Ethnicity, Customized  
[units: participants]
     
Asian     1     1     2  
Black/African American     0     1     1  
White     38     36     74  
Missing     9     11     20  
Other (Unspecified)     3     2     5  
Eastern Cooperative Oncology Performance Status (ECOG)] [1]
[units: participants]
     
0 = (Fully Active)     18     15     33  
1 (Restrictive but Ambulatory)     24     28     52  
2 (Ambulatory but Unable to Work)     7     8     15  
3 (Limited Self-Care)     0     0     0  
4 (Completely Disabled)     1     0     1  
Missing     1     0     1  
Creatinine Clearance (CrCl) [2]
[units: participants]
     
≥ 60 mL/min     32     43     75  
≥ 30 but < 60 mL/min     18     7     25  
Missing     1     1     2  
Disease Stage of DLBCL at Diagnosis [3]
[units: participants]
     
IA     4     2     6  
IB     0     0     0  
IIA     10     8     18  
IIB     9     1     10  
IIIA     8     7     15  
IIIB     2     8     10  
IVA     10     13     23  
IVB     8     11     19  
Missing     0     1     1  
Diffuse Large B-Cell Lymphoma (DLBCL) Subtypes - Germinal Center B-Cell (GCB) and non-GCB [4]
[units: participants]
     
Germinal Center B-Cell Type     23     25     48  
Non-Germinal Center B-Cell Type     28     26     54  
[1] Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living activities of the patient and determine appropriate treatment and prognosis
[2] Creatinine is a waste product from the normal breakdown of muscle tissue. As creatinine is produced, it's filtered through the kidneys and excreted in urine. Doctors measure the blood creatinine level as a test of kidney function. Participants with a CrCl (as calculated by the Cockcroft-Gault formula, utilizing actual body weight or ideal body weight, whichever was less) of ≥ 60 mL/min received a starting dose of 25 mg lenalidomide once daily. Participants with moderate renal insufficiency (ie, CrCl ≥ 30 mL/min but < 60 mL/min) received a starting dose of 10 mg lenalidomide once daily
[3] The criteria for Clinical Stage (Ann Arbor staging) are as below: I: involvement of a single nodal region. II: involvement of 2 or more lymph node regions on the same side of the diaphragm. III: involvement of lymph node regions on both sides of the diaphragm. IV: disseminated involvement of 1 or more extra-lymphatic sites with or without associated lymph node involvement. A or B: the absence of constitutional (B-type) symptoms is denoted by adding an "A" to the stage; the presence is denoted by adding a "B" to the stage.
[4] Diffuse Large B Cell Lymphoma (DLBCL) is comprised of different pathophysiological subtypes that influence patient prognosis and response to treatment. Based on immunohistochemistry (IHC), DLBCL can be classified into germinal center B-cell (GCB) and non-GCB subtypes. Patients with non-GCB have a worse prognosis compared with the GCB subtype



  Outcome Measures
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1.  Primary:   Stage 1: Percentage of Participants With an Overall Response Rate (ORR) According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999.   [ Time Frame: From Sept 2010 to the data cut-off of 4 July 2013; when all participants had reached the scheduled 16-week assessment or had progressed/died before the scheduled 16-week assessment). Median follow-up time was 6.7 and 4.7 months in each arm respectively ]

2.  Primary:   Stage 2: Progression-free Survival for Diffuse Large B-Cell Lymphoma (DLBCL) Participants   [ Time Frame: Not Applicable ]

3.  Secondary:   Stage 2: Complete Response Rate for Diffuse Large B-Cell Lymphoma (DLBCL) Participants   [ Time Frame: Not Applicable ]

4.  Secondary:   Stage 2: Overall Response Rate for Diffuse Large B-Cell Lymphoma (DLBCL) Participants   [ Time Frame: Not Applicable ]

5.  Secondary:   Stage 2: Duration of Overall Response for Diffuse Large B-Cell Lymphoma (DLBCL) Participants   [ Time Frame: Approximately 3.5 years ]

6.  Secondary:   Stage 2: Overall Survival (OS) for Diffuse Large B-Cell Lymphoma (DLBCL) Participants   [ Time Frame: Not Applicable ]

7.  Secondary:   Stage 2: Duration of Complete Response for Diffuse Large B-Cell Lymphoma (DLBCL) Participants   [ Time Frame: Not Applicable ]

8.  Secondary:   Stage 2: Overall Response Rate for Diffuse Large B-Cell Lymphoma (DLBCL) Patients With a Duration of Response Lasting ≥ 16 Weeks   [ Time Frame: Not Applicable ]

9.  Secondary:   Stage 2: Time to Progression for Diffuse Large B-Cell Lymphoma (DLBCL) Participants   [ Time Frame: Not Applicable ]

10.  Secondary:   Stage 2: Health Related Quality of Life for Diffuse Large B-Cell Lymphoma (DLBCL) Patients   [ Time Frame: Not Applicable ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Anne McClain
Organization: Celgene Corporation
phone: 1-888-260-1599
e-mail: clinicaltrialdisclosure@celgene.com


No publications provided by Celgene Corporation

Publications automatically indexed to this study:

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01197560     History of Changes
Other Study ID Numbers: CC-5013-DLC-001
Study First Received: July 29, 2010
Results First Received: July 31, 2014
Last Updated: July 31, 2014
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration