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

Purpose

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.

Condition	Intervention	Phase
Diffuse Large B-cell Lymphoma	Drug: Lenalidomide Drug: Gemcitabine Drug: Oxaliplatin Drug: Rituximab Drug: Etoposide	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Etoposide Oxaliplatin Gemcitabine Etoposide phosphate Gemcitabine hydrochloride Rituximab Lenalidomide

U.S. FDA Resources

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:

Stage 1: Overall response rate for Diffuse Large B-Cell Lymphoma (DLBCL) patients [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
Complete Response + Complete Response unconfirmed + Partial Response based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
Stage 2: Progression-free survival for Diffuse Large B-Cell Lymphoma (DLBCL) patients [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
Number of participants who survive without progressing based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).

Secondary Outcome Measures:

Stage 2: Complete response rate for Diffuse Large B-Cell Lymphoma (DLBCL) patients [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
Complete Response + Complete Response unconfirmed based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
Stage 2: Overall response rate for Diffuse Large B-Cell Lymphoma (DLBCL) patients [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
Complete Response + Complete Response unconfirmed + Partial Response based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
Stage 2: Duration of overall response for Diffuse Large B-Cell Lymphoma (DLBCL) patients [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
Length of time of overall response (Complete Response + Complete Response unconfirmed + Partial Response) based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
Stage 2: Overall survival (OS) for Diffuse Large B-Cell Lymphoma (DLBCL) patients [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
Number of participants who survive
Stage 2: Duration of complete response for Diffuse Large B-Cell Lymphoma (DLBCL) patients [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
Length of time of complete response (Complete Response + Complete Response unconfirmed) based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
Overall response rate for for Diffuse Large B-Cell Lymphoma (DLBCL) patients with a duration of response lasting ≥ 16 weeks [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
Complete Response + Complete Response unconfirmed + Partial Response for participants with a duration of response lasting ≥ 16 weeks based on the International Lymphoma Workshop Response Criteria [IWRC] (Cheson 1999).
Time to progression for Diffuse Large B-Cell Lymphoma (DLBCL) patients [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
Length of time until disease progression occurs
Number of Diffuse Large B-Cell Lymphoma (DLBCL) patients with adverse events [ Time Frame: Approximately 3.5 years. ] [ Designated as safety issue: Yes ]
Health Related Quality of Life for Diffuse Large B-Cell Lymphoma (DLBCL) patients [ Time Frame: Approximately 3.5 years ] [ Designated as safety issue: No ]
Quality of Life based on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EQ-5D assessments

Estimated Enrollment:	400
Study Start Date:	September 2010
Estimated Study Completion Date:	June 2016
Estimated Primary Completion Date:	June 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lenalidomide	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).
Active Comparator: Investigator's Choice One of the following: Lenalidomide, Gemcitabine, Oxaliplatin, Rituximab, or Etoposide	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

Arms

Assigned Interventions

Experimental: Lenalidomide

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).

Active Comparator: Investigator's Choice

One of the following:

Lenalidomide, Gemcitabine, Oxaliplatin, Rituximab, or Etoposide

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

Detailed Description:

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. Diffuse Large B-cell Lymphoma (DLBCL)is just one type of lymphoma. Within Diffuse Large B-cell Lymphoma (DLBCL) there are two different subtypes called 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 to 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically proven Diffuse Large B-Cell Lymphoma (DLBCL).
Relapsed or refractory to combination chemotherapy for Diffuse Large B-Cell Lymphoma (DLBCL) that contains rituximab and an anthracycline, and one additional combination chemotherapy or stem cell transplant.
Measurable Diffuse Large B-Cell Lymphoma (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 Diffuse Large B-Cell Lymphoma (DLBCL).
History of malignancies, other than Diffuse Large B-Cell Lymphoma (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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01197560

Show 55 Study Locations

Sponsors and Collaborators

Celgene Corporation

Investigators

Study Director:

Oliver Manzke, MD

Celgene Corporation

More Information

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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
Last Updated:	April 17, 2013
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

Keywords provided by Celgene Corporation:

Diffuse Large B-Cell Lymphoma
Non Hodgkin's Lymphoma
relapsed
refractory

relapsed/refractory
DLBCL
Diffuse Large B Cell Lymphoma

Additional relevant MeSH terms:

Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Etoposide
Etoposide phosphate
Gemcitabine
Oxaliplatin
Rituximab

Lenalidomide
Thalidomide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 22, 2013