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

• 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 ] [ Designated as safety issue: No ]

  Response was defined as participants with a complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on IWG 1999 Response Criteria for NHL as evaluated by the Independent Response Adjudication Committee (IRAC).

  Complete Response (CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers.

  CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.

  Partial Response (PR) is a 50% decrease in the sum of the products of diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes

  
  
• Stage 2: Progression-free Survival for Diffuse Large B-Cell Lymphoma (DLBCL) Participants [ Designated as safety issue: No ]
  Number of participants who survive without progressing based on the International Working Group Response Criteria [IWG].
  
  

• Stage 2: Complete Response Rate for Diffuse Large B-Cell Lymphoma (DLBCL) Participants [ Designated as safety issue: No ]

  Complete Response Rate (CR + CRu rate) was to be calculated as the proportion of participants achieving a CR or CRu using 1999 IWG Response Criteria, (Cheson, 1999).

  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).

  
  
• Stage 2: Overall Response Rate for Diffuse Large B-Cell Lymphoma (DLBCL) Participants [ Designated as safety issue: No ]

  Response was defined as participants with a complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on IWG 1999 Response Criteria for NHL (Cheson1999) as evaluated by the Independent Response Assessment Committee (IRAC).

  Complete Response (CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers.

  CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.

  Partial Response (PR) is a 50% decrease in the sum of the products of diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes

  
  
• Stage 2: Duration of Overall Response for Diffuse Large B-Cell Lymphoma (DLBCL) Participants [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
  Length of time of overall response (Complete Response + Complete Response unconfirmed + Partial Response) was to be calculated for responders as the time from documented initial response (either CR, CRu, or PR) until documented disease progression determined by CT or MRI scan, or death, whichever occurs earlier.
  
  
• Stage 2: Overall Survival (OS) for Diffuse Large B-Cell Lymphoma (DLBCL) Participants [ Designated as safety issue: No ]
  Overall Survival (OS) is defined as the time from randomization until death due to any cause.
  
  
• Stage 2: Duration of Complete Response for Diffuse Large B-Cell Lymphoma (DLBCL) Participants [ Designated as safety issue: No ]
  Duration of Complete Response was to be calculated for complete responders as the time of from documented initial complete response (either CR or CRu) until documented disease progression determined by CT or MRI scan, or death, whichever occurs earlier.
  
  
• Stage 2: Overall Response Rate for Diffuse Large B-Cell Lymphoma (DLBCL) Patients With a Duration of Response Lasting ≥ 16 Weeks [ Designated as safety issue: No ]

  Response was defined as participants with a complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on IWG Response Criteria for NHL (Cheson1999) as evaluated by the Independent Response Assessment Committee (IRAC).

  Complete Response (CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers.

  CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM.

  Partial Response (PR) is a 50% decrease in the sum of the products of diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes

  
  
• Stage 2: Time to Progression for Diffuse Large B-Cell Lymphoma (DLBCL) Participants [ Designated as safety issue: No ]
  Time to progression is defined as the time from the start of study drug therapy to the first documentation of disease progression
  
  
• Stage 2: Health Related Quality of Life for Diffuse Large B-Cell Lymphoma (DLBCL) Patients [ Designated as safety issue: No ]
  The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) is a 30-item oncology-specific questionnaire developed to assess the quality of life of cancer patients. The descriptive system EQ-5D is a generic questionnaire consisting of 3 levels within each of the 5 domains. It's is a standardized instrument for use as a measure of health outcome and provides a simple descriptive profile and a single index value for health status
  
  

This research study is for patients who have been diagnosed with Diffuse Large B-cell Lymphoma (DLBCL) that did not respond to (refractory) or that has come back after chemotherapy treatment (relapsed). Lymphoma is a cancer of a type of blood cell called lymphocytes. DLBCL is just one type of lymphoma. Within DLBCL there are two different subtypes called Germinal Center B-cell (GCB) and non-GCB which can be determined by cell surface marker tests or by gene expression tests. Scientists can look at cells and genes in the laboratory and see that the two kinds are different, but they don't know yet what the difference means. To patients and doctors these two kinds seem the same. Right now doctors don't usually do tests to find out which kind a patient has because the treatment is the same for both.

This study will have two stages, 1 and 2. The main purpose of Stage 1 is to separate patients by subtype and then test whether patients taking lenalidomide or any one of four other drugs have a better response. It is possible that lenalidomide will work better than one of the other drugs in zero, one, or both subtypes. Stage 2 will further test only the subtype(s) from Stage 1 that showed a good response to lenalidomide. The main purpose of Stage 2 is to test how long patients are disease free on lenalidomide compared to one of the four other drugs.

On 29 January 2013 the enrolment goal for the Stage 1 portion of the study was met and enrollment was stopped. The final analysis for Stage 1 was performed as of the 04 Jul 2013 data cutoff date. According to the Stage 1 results as assessed by the independent response adjudication committee (IRAC), neither subtype met the pre specified requirement to be further studied in Stage 2. Additionally, a suitable assay for the selection of participants for the Stage 2 study was not available. Therefore, on 6 January 2014, Celgene decided to not open Stage 2.