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

July 29, 2010
July 31, 2014
September 2010
July 2013   (final data collection date for primary outcome measure)
  • 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: Progression-free survival based on 1999 IWRC (Cheson 1999) [ Time Frame: Stage 2: 1 year from 122 pts. enrolled ] [ Designated as safety issue: No ]
  • Stage 1: Overall response rate (Complete Response + Complete Response unconfirmed +Partial Response) to select adequate subtypes for Stage 2 testing [ Time Frame: Stage 1: Treatment effect on best response will be evaluated after all 50 patients in a particular biomarker -defined subtype complete four cycle of treatment or have discontinued prior to four cycles of treatment. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01197560 on ClinicalTrials.gov Archive Site
  • 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
  • Complete response (Complete Response+Complete Response unconfirmed) rate [ Time Frame: Stage 2: 1 Year from 122 pts. enrolled ] [ Designated as safety issue: No ]
  • Overall Response rate (Complete Response + Complete Response Unconfirmed+Partial Response) [ Time Frame: Stage 2: 1 Year from 122 pts. enrolled ] [ Designated as safety issue: No ]
  • Duration of response (Complete Response + Complete Response Unconfirmed+ Partial Response) [ Time Frame: Stage 2: 1 Year from 122 pts. enrolled ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: When 70% of patients in stage 2 have died, are lost to follow-up or four years from last patient randomized, whichever occurs first. ] [ Designated as safety issue: No ]
  • Duration of complete response (Complete Response + Complete Response unconfirmed) [ Time Frame: 1 Year from 122 pts. enrolled ] [ Designated as safety issue: No ]
  • Overall response rate for patients with a duration of response lasting > 16 weeks [ Time Frame: 1 Year from 122 pts. enrolled ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to four years from last patient randomized. ] [ Designated as safety issue: No ]
  • Proportion of patients with adverse events in each treatment group. [ Time Frame: Up to 3 years. ] [ Designated as safety issue: Yes ]
  • Health Related Quality of Life by using EORTC QLQ-C30 and EQ-5D [ Time Frame: Every 8 weeks while on treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of Lenalidomide to Evaluate Safety and Effectiveness in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)
A Phase 2/3, Multicenter, Randomized, Open-label Study to Compare the Efficacy and Safety of Lenalidomide (Revlimid ®) Versus Investigator's Choice in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

The purpose of this study is to compare lenalidomide to a control drug and see which one delays Diffuse Large B-Cell Lymphoma (DLBCL) disease progression longer.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Diffuse Large B-cell Lymphoma
  • Drug: Lenalidomide
    Lenalidomide 25 mg orally for 21/28 days until Diffuse Large B-Cell Lymphoma (DLBCL) progressive disease. For patients with Creatinine Clearance ≥ 30 mL/min but < 60 mL/min, lenalidomide 10 mg (max escalation is 15 mg).
  • Drug: Gemcitabine
    Suggested starting doses and regimens for Gemcitabine is 1,250 mg/m2 IV days 1, 8, 15 every 28 days for 6 Cycles or 1,000 mg/m2 IV days 1 and 15 every 28 days for 6 Cycles
  • Drug: Oxaliplatin
    Suggested starting dose and regimen for Oxaliplatin is 100 mg/m2 IV day 1 for 21 days for 6 Cycles
  • Drug: Rituximab
    Suggested starting dose for Rituximab is 375 mg/m2 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)
  • Drug: Etoposide

    Suggested starting doses for Etoposide are:

    100 mg/m2 IV days 1-5 every 28 days for 6 Cycles, or 100 mg/m2 IV days 1-3 every 28 days for 6 Cycles, or 50 mg/m2 oral days 1-21 every 28 days for 6 Cycles, or 50 mg/m2 oral days 1-14 every 28 days for 6 Cycles, or 50 mg/m2 oral days 1-10 every 28 days for 6 Cycles

  • Experimental: Lenalidomide
    Intervention: Drug: Lenalidomide
  • Active Comparator: Investigator's Choice

    One of the following:

    Lenalidomide, Gemcitabine, Oxaliplatin, Rituximab, or Etoposide

    Interventions:
    • Drug: Gemcitabine
    • Drug: Oxaliplatin
    • Drug: Rituximab
    • Drug: Etoposide
Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, Pileri SA, Malik F, Macon WR, Goy A, Witzig TE, Czuczman MS. Higher response to lenalidomide in relapsed/refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype. Cancer. 2011 Nov 15;117(22):5058-66. Epub 2011 Apr 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
111
September 2015
July 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically proven Diffuse Large B-Cell Lymphoma (DLBCL).
  • Relapsed or refractory to combination chemotherapy for DLBCL that contains rituximab and an anthracycline, and one additional combination chemotherapy or stem cell transplant.
  • Measurable DLBCL disease by computed tomograph (CT) / magnetic resonance imagining (MRI).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.

Exclusion Criteria:

  • Diagnosis of lymphoma histologies other than DLBCL.
  • History of malignancies, other than DLBCL, unless the patient has been disease free for 3 years or more.
  • Eligible for autologous stem cell transplant.
  • Known seropositive for, or history of, active human immunodeficiency virus (HIV) hepatitis B virus (HBV), hepatitis C virus (HCV)
  • Neuropathy grade 4.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Italy,   France,   Spain,   Czech Republic,   United Kingdom,   Austria,   Sweden,   Australia
 
NCT01197560
CC-5013-DLC-001
Yes
Celgene Corporation
Celgene Corporation
Not Provided
Study Director: Oliver Manzke, MD Celgene Corporation
Celgene Corporation
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP