Clinical trial NCT00238238: Rituximab and/or Lenalidomide in Treating Patients With Follicular Non-Hodgkin's Lymphoma That is Not Refractory to Rituximab
Official title: A Randomized Phase II Trial of Rituximab Versus Lenalidomide (REVLIMID™, Cc-5013) (IND#73034) Versus Rituximab + Lenalidomide in Recurrent Follicular Non-Hodgkin Lymphoma (NHL) That is Not Rituximab-Refractory
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-10-13
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of non-Hodgkin's lymphoma by blocking blood flow to the cancer. Giving rituximab together with lenalidomide may kill more cancer cells. This randomized phase II trial is studying how well rituximab and/or lenalidomide work in treating patients with follicular non-Hodgkin's lymphoma that is not refractory to rituximab.

Detailed description: Outline:

This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms. Please see the "Arms" section for a description of each treatment arm. The primary and secondary objectives of the study are provided below.

Primary Objectives:

* To determine the response rate (overall and complete) after lenalidomide therapy and rituximab + lenalidomide in follicular NHL patients who have relapsed.
* To determine time to progression after lenalidomide therapy and rituximab and lenalidomide in follicular NHL patients who have relapsed.

Secondary Objectives:

* To compare the time to progression of the previous rituximab regimen to that obtained subsequently to lenalidomide therapy and rituximab + lenalidomide.
* To determine the toxicity profile of lenalidomide therapy and of rituximab and lenalidomide in follicular NHL patients who have received a previous rituximab regimen.
* To correlate Fc receptor polymorphism profiling with response to lenalidomide or rituximab + lenalidomide in previously treated patients with follicular NHL who have relapsed.
* To evaluate changes in Natural Killer (NK) cells, activated NK cells, activated T-cells and several plasma cytokines followed by rituximab therapy and correlation of observed changes to objective response rates.

After completion of study treatment, patients are followed for up to 10 years from study entry.

Eligibility criteria: * Documentation of Disease

  * Previously treated, histologically confirmed follicle center cell lymphoma, World Health Organization (WHO) classification, grade 1, 2, or 3a
  * Institutional flow cytometry or immunohistochemistry must confirm Cluster of Differentiation 20 (CD20) antigen expression.
* Prior Treatment

  * Patient must have been treated with rituximab either alone or in combination with chemotherapy.
  * Patient must have a time to progression of ≥ 6 months from last rituximab dose.
  * No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease. Maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent.
  * No prior radioimmunotherapy within 12 months of study entry.
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
* Measurable disease must be present either on physical examination or imaging studies. Non-measurable disease alone is not acceptable. Any tumor mass \>1 cm is acceptable.Lesions that are considered non-measurable include the following:

  * Bone lesions
  * Ascites
  * Pleural/pericardial effusion
  * Lymphangitis cutis/pulmonis
  * Bone marrow
* No known Central Nervous System (CNS) involvement by lymphoma.
* No known Human Immunodeficiency Virus (HIV) infection.
* Non-pregnant and non-nursing.
* Patients with a "currently active" second malignancy, other than non-melanoma skin cancers, are not eligible.
* Patients with a recent history (within 3 months of study entry) of Deep Vein Thrombosis/Pulmonary Embolism (DVT/PE) are not eligible.
* Required Initial Laboratory Values:

  * Absolute Neutrophil Count (ANC) ≥ 1000/µL
  * Platelet count ≥ 75,000/µL
  * Creatinine \< 1.5 x Upper Limit of Normal (ULN) unless attributed to lymphoma or calculated clearance \> 50 mL/min (patients on dialysis are not eligible)
  * Total Bilirubin ≤ 2 x ULN unless attributed to lymphoma or Gilbert's disease

Primary outcomes:
measure: Overall Response Rate
timeFrame: Duration of treatment (12 cycles)
measure: Time to Progression
timeFrame: Up to 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: San Diego
country: United States
facility: Kaiser Permanente Medical Office -Vandever Medical Office
state: California
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
state: Florida
city: Jupiter
country: United States
facility: Ella Milbank Foshay Cancer Center at Jupiter Medical Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Bloomington%
country: United States
facility: Illinois CancerCare - Bloomington
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare - Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare - Carthage
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare - Eureka
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic, PC
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare - Galesburg
state: Illinois
city: Havana
country: United States
facility: Illinois CancerCare - Havana
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare - Kewanee Clinic
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare - Macomb
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Monmouth
country: United States
facility: Illinois CancerCare - Monmouth
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Normal
country: United States
facility: Illinois CancerCare - Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare - Pekin
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare - Peru
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare - Princeton
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Illinois CancerCare - Spring Valley
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Saint Luke's Hospital - South
state: Kansas
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute at Saint Luke's Hospital
state: Missouri
city: Kansas City
country: United States
facility: St. Joseph Medical Center
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: Heartland Hematology Oncology Associates, Incorporated
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Lee's Summit
country: United States
facility: Saint Luke's East - Lee's Summit
state: Missouri
city: Liberty
country: United States
facility: Liberty Hospital
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Saint Joseph
country: United States
facility: Saint Joseph Oncology, Incorporated
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: Concord
country: United States
facility: New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
state: New Hampshire
city: Hooksett
country: United States
facility: New Hampshire Oncology - Hematology, PA - Hooksett
state: New Hampshire
city: Laconia
country: United States
facility: Lakes Region General Hospital
state: New Hampshire
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: East Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: Kinston
country: United States
facility: Kinston Medical Specialists
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
state: Ohio
city: Easley
country: United States
facility: Cancer Centers of the Carolinas - Easley
state: South Carolina
city: Greenville
country: United States
facility: Bon Secours St. Francis Health System
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Faris Road
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Grove Commons
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Greenwood
country: United States
facility: Self Regional Cancer Center at Self Regional Medical Center
state: South Carolina
city: Greer
country: United States
facility: Cancer Centers of the Carolinas - Greer Medical Oncology
state: South Carolina
city: Seneca
country: United States
facility: Cancer Centers of the Carolinas - Seneca
state: South Carolina
city: Spartanburg
country: United States
facility: Cancer Centers of the Carolinas - Spartanburg
state: South Carolina
city: Berlin
country: United States
facility: Mountainview Medical
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
Study officials:
affiliation: Weill Medical College of Cornell University
name: John P. Leonard, MD
role: STUDY_CHAIR
References:
citation: Leonard JP, Jung SH, Johnson J, Pitcher BN, Bartlett NL, Blum KA, Czuczman M, Giguere JK, Cheson BD. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). J Clin Oncol. 2015 Nov 1;33(31):3635-40. doi: 10.1200/JCO.2014.59.9258. Epub 2015 Aug 24.