Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00068250
First received: September 10, 2003
Last updated: June 21, 2013
Last verified: June 2013
  Purpose

RATIONALE: Drugs used in chemotherapy such as methotrexate and temozolomide use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining methotrexate, temozolomide, and rituximab with radiation therapy may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of temozolomide when given together with methotrexate and rituximab followed by radiation therapy and to see how well they work in treating patients with primary central nervous system lymphoma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Lymphoma
Biological: rituximab
Drug: methotrexate
Drug: temozolomide
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For Primary Central Nervous System Lymphoma

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Toxicity rate (Phase I) [ Time Frame: From start of treatment to 10 weeks. ] [ Designated as safety issue: Yes ]
  • Overall survival rate at 2 years (Phase ll) [ Time Frame: Death or last follow-up. Anaylsis occurs after all patients have been potentially followed for 2 years. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pre-irradiation chemotherapy tumor response rate (Phase II) [ Time Frame: From start of treatment to 10 weeks. ] [ Designated as safety issue: No ]
  • Progression-free survival (Phase II) [ Time Frame: From randomization to date of progression, death or last follow-up. Analysis occurs at the same time as the primary outcome analysis. ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: July 2003
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I: Temozolomide (TMZ) 100mg
Phase I: Temozolomide 100mg
Biological: rituximab Drug: methotrexate Drug: temozolomide Radiation: radiation therapy
Experimental: Phase I: Temozolomide (TMZ) 150 mg
Phase I: Temozolomide 150 mg
Biological: rituximab Drug: methotrexate Drug: temozolomide Radiation: radiation therapy
Experimental: Phase I: Temozolomide (TMZ) 200 mg
Phase I: Temozolomide 200 mg
Biological: rituximab Drug: methotrexate Drug: temozolomide Radiation: radiation therapy
Experimental: Phase II: Temozolomide (TMZ) 100 mg
Phase II: Temozolomide 100 mg
Biological: rituximab Drug: methotrexate Drug: temozolomide Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of temozolomide in combination with methotrexate and rituximab before fractionated whole brain radiotherapy in patients with primary central nervous system lymphoma.
  • Compare the 2-year survival rate of patients receiving this chemotherapy regimen before radiotherapy and temozolomide after radiotherapy to that of patients treated on protocol RTOG-9310.
  • Compare the tumor response rates of patients treated with this chemotherapy regimen before radiotherapy to that of patients treated on Radiation Therapy Oncology Group (RTOG), RTOG-9310.
  • Determine the progression-free survival of patients treated with this regimen.
  • Determine the acute and long-term neurologic toxicity of this regimen in these patients.
  • Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a phase I dose-escalation study of temozolomide in combination with methotrexate and rituximab before radiotherapy, followed by a phase II study.

Phase I

  • Pre-radiotherapy chemotherapy: Patients receive rituximab IV 3 days prior to the first course of methotrexate. Patients then receive methotrexate IV over 4 hours on weeks 1, 3, 5, 7, and 9 (for a total of 5 doses). Patients also receive oral temozolomide daily for 5 days on weeks 4 and 8.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 0 of 3 or 1 of 6 patients experience dose-limiting toxicity.

  • Radiotherapy: Patients undergo whole brain radiotherapy daily for 5 days on weeks 11, 12, and 13.
  • Post-radiotherapy chemotherapy: Patients receive oral temozolomide once daily on days 1-5 beginning at week 14. Treatment repeats every 28 days for 10 courses in the absence of unacceptable toxicity.

Phase II

  • Patients receive treatment as in phase I at the MTD of temozolomide. Treatment continues in the absence of unacceptable toxicity.

Quality of life is assessed at baseline, at weeks 10 and 13, every 2 months during post-radiotherapy temozolomide therapy, at the end of therapy, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 52-64 patients (up to 18 patients for phase I and 46 patients for phase II) will be accrued for this study within 19 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Cytologically confirmed primary central nervous system (CNS) lymphoma

    • Based on positive biopsy, cerebrospinal fluid, or vitreous cytology (in association with measurable intraparenchymal tumor)
    • B-cell type
    • Cluster of Differentiation antigen (CD20)+ disease
    • Cytology must demonstrate lymphoma OR an immunohistochemical diagnosis of malignant lymphocytes with a monoclonal lymphocytic population
  • No evidence of systemic lymphoma

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • At least 8 weeks

Hematopoietic

  • Absolute granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin no greater than 2 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) no greater than 2 times ULN
  • Alkaline phosphatase no greater than 2 times ULN
  • No active hepatitis B

Renal

  • Creatinine clearance at least 50 mL/min
  • No renal insufficiency

Other

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No HIV positivity
  • No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No history of idiopathic sensitivity to any of the drugs in this study
  • No active infection
  • No known anaphylaxis or Immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy to the brain, head, or neck

Surgery

  • No prior organ transplantation
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00068250

Locations
United States, Florida
Baptist Cancer Institute - Jacksonville
Jacksonville, Florida, United States, 32207
Integrated Community Oncology Network at Southside Cancer Center
Jacksonville, Florida, United States, 32207
Integrated Community Oncology Network
Jacksonville Beach, Florida, United States, 32250
Baptist Medical Center South
Jascksonville, Florida, United States, 32258
Integrated Community Oncology Network - Orange Park
Orange Park, Florida, United States, 32073
Florida Cancer Center - Palatka
Palatka, Florida, United States, 32177
Flagler Cancer Center
Saint Augustine, Florida, United States, 32086
United States, Michigan
Borgess Medical Center
Kalamazoo, Michigan, United States, 49001
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007-3731
United States, Missouri
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, Nevada
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
United States, New Jersey
John F. Kennedy Medical Center
Edison, New Jersey, United States, 08818
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Oregon
Providence Milwaukie Hospital
Milwaukie, Oregon, United States, 97222
Providence Cancer Center at Providence Portland Medical Center
Portland, Oregon, United States, 97213-2967
Providence St. Vincent Medical Center
Portland, Oregon, United States, 97225
CCOP - Columbia River Oncology Program
Portland, Oregon, United States, 97225
United States, Pennsylvania
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Philadelphia, Pennsylvania, United States, 19107-5541
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Utah
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
Murray, Utah, United States, 84157
Utah Valley Regional Medical Center - Provo
Provo, Utah, United States, 84604
United States, Washington
Southwest Washington Medical Center Cancer Center
Vancouver, Washington, United States, 98668
United States, Wisconsin
Community Memorial Hospital Cancer Care Center
Menomonee Falls, Wisconsin, United States, 53051
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: Jon Glass, MD Kimmel Cancer Center (KCC)
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00068250     History of Changes
Other Study ID Numbers: RTOG-0227, CDR0000301563
Study First Received: September 10, 2003
Last Updated: June 21, 2013
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
primary central nervous system non-Hodgkin lymphoma
primary central nervous system Hodgkin lymphoma

Additional relevant MeSH terms:
Lymphoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Nervous System Diseases
Antibodies, Monoclonal
Methotrexate
Rituximab
Temozolomide
Dacarbazine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on April 15, 2014