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

Information source: Radiation Therapy Oncology Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Chemotherapeutic Agent Toxicity; Cognitive/Functional Effects; Lymphoma; Neurotoxicity; Radiation Toxicity

Intervention: rituximab (Biological); cytarabine (Drug); methotrexate (Drug); procarbazine hydrochloride (Drug); vincristine sulfate (Drug); whole-brain radiation therapy (Radiation)

Phase: Phase 2

Status: Recruiting

Sponsored by: Radiation Therapy Oncology Group

Official(s) and/or principal investigator(s):
Antonio Omuro, MD, Principal Investigator, Affiliation: Memorial Sloan Kettering Cancer Center

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.

Clinical Details

Official title: Phase II Randomized Study of Rituximab, Methotrexate, Procarbazine, Vincristine, and Cytarabine With and Without Low-Dose Whole-Brain Radiotherapy for Primary Central Nervous System Lymphoma

Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Progression free survival (PFS) defined as the interval from randomization to progression or death, whichever occurs first

Secondary outcome:

Overall survival (OS) defined as the interval from randomization to death due to any cause

Response rate (partial response or complete response)

Quality of life measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core/Brain Cancer Module (QLQ-C30/BCM20)

Neurocognitive function measured by the Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test Part A, Trail Making Test Part B, Controlled Oral Word Association Test (COWAT)

Detailed 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.

- Arm I: Patients receive rituximab IV over 5 hours or per institutional guidelines on

days 1 and 15, methotrexate IV over 2 hours on days 2 and 16, vincristine sulfate IV on days 2 and 16 (courses 1 and 2 only), and procarbazine hydrochloride orally (PO) on days 2-8. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive consolidation therapy comprising cytarabine IV over 3 hours on days 1-2. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive rituximab, methotrexate, vincristine sulfate, and procarbazine

hydrochloride as in arm I. After completing chemotherapy (2-5 weeks later), patients without progressive disease undergo low-dose whole-brain radiotherapy once daily, 5 days a week, for approximately 2. 5 weeks (13 fractions total). Patients then receive consolidation cytarabine as in arm I. Patients may undergo blood and buccal sample collection for future correlative studies. Paraffin-embedded tissue block of primary tumor or a core tumor tissue punched from the tissue block, and cerebrospinal fluid may also be collected. Patients may also complete the Hopkins Verbal Learning Test-Revised (HVLT-R), the Trail Making Test Part A and Part B, the Controlled Oral Word Association Test (COWAT), and the Quality of Life (QOL) questionnaires at baseline and periodically during study. After completion of study therapy, patients are followed up every 2 months for 2 years and then every 6 months for 3 years.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- B-cell non-Hodgkin lymphoma (NHL) involving the brain, as demonstrated by contrasted

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 NHL

- Brain biopsy

- Patients in whom the type of lymphoma could not be determined or is unknown

(e. g., not enough tissue for further analysis) are assumed to have a B-cell lymphoma and are eligible

- 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 NHL as demonstrated by a CT scan of the chest, abdomen, and

pelvis within 6 weeks prior to registration

- Bone marrow biopsy is not required for registration but must be obtained prior

to start of treatment PATIENT CHARACTERISTICS:

- History and physical examination within 6 weeks of registration

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

exception:

- 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

- Absolute neutrophil count (ANC) ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin (Hgb) ≥ 8. 0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8. 0

g/dL is acceptable)

- Bilirubin < 2. 0 mg/dL

- Aspartate aminotransferase (AST) < 2. 5 times upper limit of normal

- Serum creatinine < 1. 5 mg/dL

- Calculated creatinine clearance (CrCl) > 50 cc/min (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 be able to swallow pills

- Patient must have documentation of negative HIV-1 testing within 6 weeks prior to

study registration

- No 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)

- No 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

- 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

- No prior allergic reaction to any of the study drugs involved in this protocol

PRIOR CONCURRENT THERAPY:

- No prior treatment with chemotherapy or radiotherapy for lymphoma or chronic

lymphocytic leukemia

- Prior chemotherapy for a different cancer is allowable

- No prior cranial irradiation

- No concurrent intensity-modulated radiotherapy

Locations and Contacts

Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel; Active, not recruiting

The Kirklin Clinic at Acton Road, Birmingham, Alabama 35243, United States; Active, not recruiting

University of Alabama at Birmingham, Birmingham, Alabama 35294, United States; Active, not recruiting

Arizona Oncology-Deer Valley Center, Phoenix, Arizona 85027, United States; Active, not recruiting

Arizona Oncology Services Foundation, Scottsdale, Arizona 85260, United States; Recruiting
David G. Brachman, Phone: 800-360-6371
David G. Brachman, Principal Investigator

Kaiser Permanente-Rancho Cordova Cancer Center, Rancho Cardova, California 95670, United States; Recruiting
Samantha A. Seaward, Phone: 626-564-3455
Samantha A. Seaward, Principal Investigator

Rohnert Park Cancer Center, Rohnert Park, California 94928, United States; Recruiting
Samantha A. Seaward, Phone: 626-564-3455
Samantha A. Seaward, Principal Investigator

The Permanente Medical Group-Roseville Radiation Oncology, Roseville, California 95678, United States; Recruiting
Samantha A. Seaward, Phone: 626-564-3455
Samantha A. Seaward, Principal Investigator

South Sacramento Cancer Center, Sacramento, California 95823, United States; Recruiting
Samantha A. Seaward, Phone: 626-564-3455
Samantha A. Seaward, Principal Investigator

Kaiser Permanente Medical Center - Santa Clara, Santa Clara, California 95051, United States; Recruiting
Samantha A. Seaward, Phone: 626-564-3455
Samantha A. Seaward, Principal Investigator

Kaiser Permanente Cancer Treatment Center, South San Francisco, California 94080, United States; Recruiting
Samantha A. Seaward, Phone: 626-564-3455
Samantha A. Seaward, Principal Investigator

Penrose-Saint Francis Healthcare, Colorado Springs, Colorado 80907, United States; Recruiting
Alan T. Monroe, Phone: 888-785-6789
Alan T. Monroe, Principal Investigator

Cancer Specialists of North Florida-Beaches, Jacksonville Beach, Florida 32250, United States; Withdrawn

Cancer Specialists of North Florida-Southside, Jacksonville, Florida 32207, United States; Withdrawn

Edna Williams Cancer Center at the Baptist Cancer Institute, Jacksonville, Florida 32207, United States; Withdrawn

Cancer Specialists of North Florida-Baptist South, Jascksonville, Florida 32258, United States; Withdrawn

Cancer Specialists of North Florida-Orange Park, Orange Park, Florida 32073, United States; Withdrawn

Cancer Specialists of North Florida-Putnam, Palatka, Florida 32177, United States; Withdrawn

Cancer Specialists of North Florida-Saint Augustine, Saint Augustine, Florida 32086, United States; Withdrawn

H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, United States; Recruiting
Peter A. Forsyth, Phone: 800-456-7121, Email: canceranswers@moffitt.org
Peter A. Forsyth, Principal Investigator

Saint Alphonsus Regional Medical Center, Boise, Idaho 83706, United States; Recruiting
Samir Narayan, Phone: 734-712-4673
Samir Narayan, Principal Investigator

Northwestern University, Chicago, Illinois 60611, United States; Recruiting
Jeffrey J. Raizer, Phone: 312-695-1301, Email: cancer@northwestern.edu
Jeffrey J. Raizer, Principal Investigator

Rush University Medical Center, Chicago, Illinois 60612, United States; Recruiting
Reem Karmali, Phone: 312-942-5498, Email: clinical_trials@rush.edu
Reem Karmali, Principal Investigator

Loyola University Medical Center, Maywood, Illinois 60153, United States; Terminated

Cadence Cancer Center in Warrenville, Warrenville, Illinois 60555, United States; Recruiting
Vinai Gondi, Phone: 630-352-5300
Vinai Gondi, Principal Investigator

Maine Medical Center-Bramhall Campus, Portland, Maine 04102, United States; Recruiting
Ian J. Bristol, Phone: 207-396-8090, Email: wrighd@mmc.org
Ian J. Bristol, Principal Investigator

Maine Medical Center- Scarborough Campus, Scarborough, Maine 04074, United States; Recruiting
Ian J. Bristol, Phone: 207-396-8090, Email: wrighd@mmc.org
Ian J. Bristol, Principal Investigator

University of Maryland/Greenebaum Cancer Center, Baltimore, Maryland 21201, United States; Recruiting
Navesh K. Sharma, Phone: 800-888-8823
Navesh K. Sharma, Principal Investigator

Saint Joseph Mercy Hospital, Ann Arbor, Michigan 48106-0995, United States; Recruiting
Samir Narayan, Phone: 734-712-4673
Samir Narayan, Principal Investigator

West Michigan Cancer Center, Kalamazoo, Michigan 49007, United States; Recruiting
Raymond S. Lord, Phone: 269-373-7458
Raymond S. Lord, Principal Investigator

Nevada Cancer Research Foundation CCOP, Las Vegas, Nevada 89106, United States; Recruiting
John A. Ellerton, Phone: 702-384-0013
John A. Ellerton, Principal Investigator

Memorial Sloan Kettering Cancer Center at Basking Ridge, Basking Ridge, New Jersey 07920, United States; Active, not recruiting

Memorial Sloan Kettering Cancer Center Commack, Commack, New York 11725, United States; Active, not recruiting

Columbia University Medical Center, New York, New York 10032, United States; Active, not recruiting

Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States; Recruiting
Antonio M. Omuro, Phone: 212-639-7202
Antonio M. Omuro, Principal Investigator

University of Rochester, Rochester, New York 14642, United States; Recruiting
Yuhchyau Chen, Phone: 585-275-5830
Yuhchyau Chen, Principal Investigator

University of Cincinnati, Cincinnati, Ohio 45267, United States; Recruiting
Kevin P. Redmond, Phone: 513-558-4553, Email: uchealthnews@uc.edu
Kevin P. Redmond, Principal Investigator

Case Western Reserve University, Cleveland, Ohio 44106, United States; Recruiting
Erin S. Murphy, Phone: 866-223-8100
Erin S. Murphy, Principal Investigator

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States; Recruiting
Erin S. Murphy, Phone: 866-223-8100
Erin S. Murphy, Principal Investigator

University Pointe, West Chester, Ohio 45069, United States; Recruiting
Kevin P. Redmond, Phone: 513-558-4553, Email: uchealthnews@uc.edu
Kevin P. Redmond, Principal Investigator

Natalie Warren Bryant Cancer Center at Saint Francis, Tulsa, Oklahoma 74136, United States; Withdrawn

Geisinger Medical Center, Danville, Pennsylvania 17822-2001, United States; Recruiting
Thomas J. Gergel, Phone: 570-271-5251
Thomas J. Gergel, Principal Investigator

American College of Radiology Imaging Network, Philadelphia, Pennsylvania 19103, United States; Recruiting
Antonio M. Omuro, Phone: 212-639-7523, Email: omuroa@mskcc.org
Antonio M. Omuro, Principal Investigator

Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107, United States; Recruiting
Jon Glass, Phone: 215-955-6084
Jon Glass, Principal Investigator

Geisinger Wyoming Valley, Wilkes-Barre, Pennsylvania 18711, United States; Recruiting
Thomas J. Gergel, Phone: 570-271-5251
Thomas J. Gergel, Principal Investigator

M D Anderson Cancer Center, Houston, Texas 77030, United States; Active, not recruiting

M D Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Ivo W. Tremont, Phone: 504-340-6976
Ivo W. Tremont, Principal Investigator

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, United States; Recruiting
Chul S. Ha, Phone: 210-567-0653, Email: che@uthscsa.edu
Chul S. Ha, Principal Investigator

Community Memorial Hospital, Menomonee Falls, Wisconsin 53051, United States; Recruiting
Joseph A. Bovi, Phone: 414-805-4380
Joseph A. Bovi, Principal Investigator

Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States; Recruiting
Joseph A. Bovi, Phone: 414-805-4380
Joseph A. Bovi, Principal Investigator

Waukesha Memorial Hospital - ProHealth Care, Waukesha, Wisconsin 53188, United States; Recruiting
Wingate F. Clapper, Phone: 262-928-7632
Wingate F. Clapper, Principal Investigator

Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: September 2011
Last updated: March 20, 2015

Page last updated: August 23, 2015

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