Non Hodgkin Lymphoma Clinical Trial

Rituximab, Methotrexate, Vincristine Sulfate, Procarbazine Hydrochloride, and Cytarabine With or Without Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma

Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as methotrexate, vincristine sulfate, procarbazine hydrochloride, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill cancer cells. It is not yet know whether rituximab and combination chemotherapy are more effective when given with or without radiation therapy in treating patients with primary central nervous system lymphoma.

PURPOSE: This randomized phase II trial studies how well giving rituximab and combination chemotherapy with or without radiation therapy works in treating patients with primary central nervous system lymphoma.

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Full Description

OBJECTIVES:

Primary

To determine median progression-free survival (PFS) in both arms on an intent-to-treat basis.

Secondary

To determine overall survival (OS) defined as the interval from randomization to death due to any cause.
To determine treatment-related neurotoxicity rates and disease-related cognitive deterioration in each arm, through the following methods: prospective formal neuropsychological evaluation, utilizing competing-risk methodology to account for death as a competing risk to neurotoxicity or cognitive deterioration from relapsed tumor burden/salvage treatment and incidence of clinically defined neurotoxicity as per investigator's assessment.
To determine if there exists differences between the two treatment arms in terms of health-related quality-of-life and symptoms over time.
To determine response (partial response (PR) and complete response (CR)) rate after methotrexate-based chemotherapy and after consolidation whole-brain radiotherapy (WBRT).
To determine chemotherapy-related toxicity, measured by Common Toxicity Criteria for Adverse Effects (CTCAE), v.4.0.

OUTLINE: This is a multicenter study. Patients are stratified according to Memorial Sloan-Kettering Cancer Center recursive-partitioning analysis (RPA) classification for primary central nervous system lymphoma on age and Karnofsky performance status (KPS) (Class 1: age ≤ 50 years vs Class 2: age > 50 years and KPS ≥ 70% vs Class 3: age > 50 years and KPS < 70%). Patients are randomized to 1 of 2 treatment arms.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

B-cell non-Hodgkin's lymphoma(NHL) involving the brain, as demonstrated by contrast-enhanced Magnetic resonance imaging (MRI) and histologic confirmation by one of the following within 6 weeks prior to registration:

A positive cerebral spinal fluid (CSF) cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers
A biopsy of the vitreous or uvea demonstrating non-Hodgkin's lymphoma
Brain biopsy

Note: Patients in whom the type of lymphoma could not be determined or is unknown (eg, not enough tissue for further analysis) are assumed to have a B cell lymphoma and are eligible.

The patient must agree to submit tissue (i.e., the original H/E stained slides and immunohistochemistry studies) for central pathology review post-registration.
No evidence of systemic non-Hodgkin lymphoma as demonstrated by a computed tomography (CT) scan of the chest, abdomen and pelvis within 6 weeks prior to registration (Note: Bone marrow biopsy is not required for registration but must be obtained prior to start of treatment.)
Age ≥ 18
History and physical examination within 6 weeks of registration

Karnofsky performance status (KPS) equal to 50 or higher, with the following exception

• Patients with KPS 30 to 50 are eligible if the reason for the poor performance status is neurologic deficit from primary central nervous system (CNS) lymphoma. (Patients with KPS 30 to 50 due to reasons other than primary CNS lymphoma are ineligible. Patients with KPS under 30 for any reason are ineligible)

Patient must have documentation of negative HIV-1 testing within 6 weeks prior to study registration (Separate counseling and consent as per institutional guidelines)

Complete blood count (CBC)/differential obtained within 2 weeks prior to study registration, with adequate bone marrow function defined as follows:

Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
Platelets ≥ 100,000 cells/mm3;
Hemoglobin (Hgb) ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.);

Adequate liver function within 2 weeks prior to study registration, defined as follows:

Bilirubin < 2.0 mg/dl
Aspartate aminotransferase (AST) <2.5 times upper limit of normal

Adequate renal function within 2 weeks prior to study registration, defined as follows

Serum creatinine < 1.5 mg/dl
Calculated creatinine clearance (CrCl) > 50cc/min/1.73m2, using the Cockcroft-Gault equation, as follows:

Male: CrCl (ml/min) = (140-age) X (Actual weight in kg) / 72 x serum Creatinine (mg/dl).

Female: CrCl (ml/min) = (140-age) X (Actual weight in kg) X 0.85 / 72 x serum Creatinine (mg/dl).

Note: A measured CrCl from a 24 hour urine collection may also be used.

Women of childbearing potential and male participants must agree to practice adequate contraception during therapy
Patient must provide study-specific informed consent prior to study registration
Patient must be able to swallow pills.

Exclusion Criteria:

Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
Prior treatment with chemotherapy or radiotherapy for lymphoma or chronic lymphocytic leukemia; note that prior chemotherapy for a different cancer is allowable; see section 1
Prior cranial irradiation

Severe, active co-morbidity, defined as follows:

Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
Transmural myocardial infarction within the last 6 months;
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.
Known pre-existing immunodeficiency as seen in organ transplant recipient.
Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
Prior allergic reaction to any of the study drugs involved in this protocol.

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

91

Study ID:

NCT01399372

Recruitment Status:

Completed

Sponsor:

Radiation Therapy Oncology Group

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There are 44 Locations for this study

See Locations Near You

University of Alabama at Birmingham Cancer Center
Birmingham Alabama, 35233, United States
The Kirklin Clinic at Acton Road
Birmingham Alabama, 35243, United States
Saint Joseph's Hospital and Medical Center
Phoenix Arizona, 85013, United States
Arizona Oncology-Deer Valley Center
Phoenix Arizona, 85027, United States
Arizona Oncology Services Foundation
Scottsdale Arizona, 85260, United States
Fresno Cancer Center
Fresno California, 93720, United States
Kaiser Permanente-Rancho Cordova Cancer Center
Rancho Cordova California, 95670, United States
Rohnert Park Cancer Center
Rohnert Park California, 94928, United States
The Permanente Medical Group-Roseville Radiation Oncology
Roseville California, 95678, United States
South Sacramento Cancer Center
Sacramento California, 95823, United States
Kaiser Permanente Medical Center - Santa Clara
Santa Clara California, 95051, United States
Kaiser Permanente Cancer Treatment Center
South San Francisco California, 94080, United States
Penrose-Saint Francis Healthcare
Colorado Springs Colorado, 80907, United States
Moffitt Cancer Center
Tampa Florida, 33612, United States
Saint Alphonsus Cancer Care Center-Boise
Boise Idaho, 83706, United States
Northwestern University
Chicago Illinois, 60611, United States
Rush University Medical Center
Chicago Illinois, 60612, United States
Loyola University Medical Center
Maywood Illinois, 60153, United States
Cadence Cancer Center in Warrenville
Warrenville Illinois, 60555, United States
Maine Medical Center-Bramhall Campus
Portland Maine, 04102, United States
Maine Medical Center- Scarborough Campus
Scarborough Maine, 04074, United States
University of Maryland/Greenebaum Cancer Center
Baltimore Maryland, 21201, United States
Saint Joseph Mercy Hospital
Ann Arbor Michigan, 48106, United States
West Michigan Cancer Center
Kalamazoo Michigan, 49007, United States
Nevada Cancer Research Foundation CCOP
Las Vegas Nevada, 89106, United States
Dartmouth Hitchcock Medical Center
Lebanon New Hampshire, 03756, United States
Memorial Sloan Kettering Cancer Center at Basking Ridge
Basking Ridge New Jersey, 07920, United States
Memorial Sloan Kettering Cancer Center Commack
Commack New York, 11725, United States
Columbia University Medical Center
New York New York, 10032, United States
Memorial Sloan-Kettering Cancer Center
New York New York, 10065, United States
University of Rochester
Rochester New York, 14642, United States
University of Cincinnati
Cincinnati Ohio, 45267, United States
Case Western Reserve University
Cleveland Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland Ohio, 44195, United States
University Pointe
West Chester Ohio, 45069, United States
Geisinger Medical Center
Danville Pennsylvania, 17822, United States
American College of Radiology Imaging Network
Philadelphia Pennsylvania, 19103, United States
Thomas Jefferson University Hospital
Philadelphia Pennsylvania, 19107, United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre Pennsylvania, 18711, United States
M D Anderson Cancer Center CCOP Research Base
Houston Texas, 77030, United States
M D Anderson Cancer Center
Houston Texas, 77030, United States
Community Memorial Hospital
Menomonee Falls Wisconsin, 53051, United States
Froedtert and the Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States
Waukesha Memorial Hospital
Waukesha Wisconsin, 53188, United States
Tel Aviv Sourasky Medical Center
Tel Aviv , 64239, Israel

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

91

Study ID:

NCT01399372

Recruitment Status:

Completed

Sponsor:


Radiation Therapy Oncology Group

How clear is this clinincal trial information?

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