Immunotherapy Combined With Chemotherapy Followed by Radiation Therapy and Chemotherapy in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00059956

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Drugs used in immunotherapy such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells, and may make cancer cells more sensitive to chemotherapy. Radiation therapy uses high-energy x-rays to damage cancer cells. Giving lower doses of radiation may cause less damage to normal tissue.

PURPOSE: Phase II trial to study the effectiveness of combining immunotherapy with combination chemotherapy followed by low-dose radiation therapy and cytarabine in treating patients who have newly diagnosed primary central nervous system lymphoma.

Condition	Intervention	Phase
Lymphoma	Biological: rituximab Drug: cytarabine Drug: methotrexate Drug: procarbazine hydrochloride Drug: vincristine sulfate Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Pilot Study of Combined Immunochemotherapy Followed by Reduced Dose RT for Patients With Newly Diagnosed PCNSL

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Vincristine Methotrexate Cytarabine hydrochloride Rituximab Cytarabine Procarbazine hydrochloride Procarbazine Vincristine sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Treatment related toxicity assessed by NCI CTC [ Designated as safety issue: Yes ]
Disease-free survival at 1 year [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate assessed radiographically every 2 months [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]

Study Start Date:

August 2002

Detailed Description:

OBJECTIVES:

Determine the efficacy of induction immunochemotherapy comprising rituximab, methotrexate, procarbazine, and vincristine followed by reduced-dose radiotherapy and consolidation cytarabine in patients with newly diagnosed primary central nervous system lymphoma.
Determine the 2-year and overall disease-free survival of patients treated with this regimen.
Determine the progression-free and overall survival of patients treated with this regimen.
Determine the acute treatment-related toxicity and safety of this regimen in these patients.
Determine the initial response rate of patients treated with immunochemotherapy.
Determine the relapse rate after complete response in patients treated with this regimen.
Determine the neuro-cognitive outcome in patients treated with this regimen.

OUTLINE: This is a multicenter, pilot study.

Induction immunochemotherapy: Patients receive rituximab IV over 5 hours on day 1 and methotrexate IV over 2 hours and vincristine IV over several minutes on day 2. Patients also receive oral procarbazine on days 2-8 during courses 1, 3, and 5. Treatment repeats every 2 weeks for 5 courses in the absence of disease progression or unacceptable toxicity. Patients with a partial response after 5 courses may receive an additional 2 courses.
Radiotherapy: Beginning 3-5 weeks after completion of induction immunochemotherapy, patients undergo radiotherapy daily 5 days a week for 3-6 weeks.
Consolidation chemotherapy: Patients receive cytarabine IV over 3 hours on days 1 and 2. Treatment repeats every 28 days for a total of 2 courses.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 3 years.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed primary non-Hodgkin's lymphoma by brain biopsy
- Patients who have an inconclusive biopsy or who are not a candidate for biopsy are eligible provided they have a typical cranial MRI or CT scan* AND meet at least 1 of the following criteria:
  - Positive cerebrospinal fluid cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers
  - Biopsy of the vitreous or uvea demonstrating non-Hodgkin's lymphoma NOTE: *Typical MRI or CT scan is defined as the presence of hypo-, iso-, or hyperdense parenchymal contrast-enhancing (usually homogeneously) mass lesion(s)
HIV-1 negative
Normal or negative pretreatment systemic evaluation including the following examinations:
- Bone marrow aspirate and biopsy
- CT scans of the chest, abdomen, and pelvis

PATIENT CHARACTERISTICS:

Age

Any age

Performance status

Not specified

Life expectancy

At least 8 weeks

Hematopoietic

WBC at least 4,000/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin no greater than 2.0 mg/dL
SGOT no greater than 2 times upper limit of normal

Renal

Creatinine no greater than 1.5 mg/dL OR
Creatinine clearance at least 50 mL/min

Other

Not pregnant
Fertile patients must use effective contraception during and for 6 months after study participation
No other active primary malignancy except basal cell skin cancer or carcinoma in situ of the cervix
No pre-existing immunodeficiency (e.g., renal transplantation recipient)
Must maintain a tyramine-free diet (i.e., free of alcohol and certain cheeses) during procarbazine administration

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy for CNS lymphoma

Endocrine therapy

Not specified

Radiotherapy

No prior cranial radiotherapy

Surgery

Not specified

Other

No citrus fruit, citrus fruit juices, or ascorbic acid supplements during and for 72 hours after methotrexate administration

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00059956

Locations

United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, Kentucky
Kentuckiana Cancer Institute, PLLC
Louisville, Kentucky, United States, 40202
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Vermont
Vermont Cancer Center at University of Vermont
Burlington, Vermont, United States, 05401-3498
United States, Virginia
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22908

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Lauren E. Abrey, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000298992, MSKCC-01146
Study First Received:	May 6, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00059956 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

primary central nervous system lymphoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents
Lymphoma
Nucleic Acid Synthesis Inhibitors
Cytarabine

Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Rituximab
Mitosis Modulators
Vincristine
Enzyme Inhibitors
Antimitotic Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms

ClinicalTrials.gov processed this record on November 09, 2009