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Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed Primary CNS Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00416819
First received: December 27, 2006
Last updated: October 1, 2012
Last verified: October 2012
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This clinical trial is studying the side effects and best ways to give combination chemotherapy together with rituximab in treating patients with newly diagnosed primary CNS lymphoma.


Condition Intervention
Brain and Central Nervous System Tumors
Lymphoma
 Biological: filgrastim
Biological: rituximab
Drug: cytarabine
Drug: etoposide phosphate
Drug: leucovorin calcium
Drug: methotrexate
Drug: temozolomide

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intensive Chemotherapy and Immunotherapy in Patients With Newly Diagnosed Primary CNS Lymphoma: A Pilot Study

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • rate of toxicity in patients with untreated primary CNS lymphoma [ Time Frame: up to 8 months ] [ Designated as safety issue: Yes ]
    Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.


Secondary Outcome Measures:
  • Efficacy in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate. [ Time Frame: up to 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10
Study Start Date: September 2003
Estimated Study Completion Date: December 2014
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: methotrexate, leucovorin calcium, rituximab, and temozolomide
Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.
 Biological: filgrastim Biological: rituximab Drug: cytarabine Drug: etoposide phosphate Drug: leucovorin calcium Drug: methotrexate Drug: temozolomide

Detailed Description:

OBJECTIVES:

Primary

  • Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.

Secondary

  • Determine the efficacy of this regimen, in terms of the 4-month and 12-month complete and best response rate, in these patients.
  • Determine the progression-free and overall survival of patients treated with this regimen.
  • Determine the percentage of patients experiencing toxicity or neurotoxicity due to this regimen.
  • Determine the treatment-related mortality rate in patients treated with this regimen.
  • Document the neurocognitive changes in these patients using the Mini-Mental Status Examination during the first year of treatment with this regimen.

OUTLINE: This is a pilot, multicenter study.

  • Induction therapy: Patients receive high-dose methotrexate IV over 4 hours on days 1,15, 29, 43, 57, 71, and 99; leucovorin calcium IV every 6 hours on days 2-4, 16-18, 30-32, 44-46, 58-60, 72-74, and 100-102; oral temozolomide on days 7-11, 35-39, 63-67, 91-95, and 119-123; and rituximab IV on days 3, 17, 31, 45, 59, and 74. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response proceed to consolidation therapy.
  • Consolidation therapy I: Beginning 3-4 weeks after completing induction therapy, patients receive high-dose methotrexate IV over 4 hours on day 1, leucovorin calcium IV every 6 hours on days 2-4, and oral temozolomide on days 7-11.
  • Consolidation therapy II: Beginning 3-5 weeks after completing consolidation therapy I, patients receive cytarabine IV over 2 hours twice daily and etoposide phosphate IV continuously on days 1-4 and filgrastim (G-CSF) subcutaneously beginning on day 14 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 10 patients will be accrued to this study.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed untreated primary CNS lymphoma (PCNSL) confirmed by 1 of the following methods:

    • Brain biopsy or resection

      • Patients diagnosed with T-cell PCNSL allowed but will not receive rituximab on study

    • Cerebrospinal fluid (CSF) cytology

      • Positive CSF cytology with or without measurable intracranial disease

    • Vitreal biopsy

      • Histologic confirmation of vitreal lymphoma with measurable intracranial tumor

  • No evidence of systemic non-Hodgkin's lymphoma

    • CT scan of chest, abdomen, and pelvis or bone marrow biopsy negative for extracerebral source of lymphoma
  • No evidence of pleural effusions or ascites
  • MRI of brain and spine (plus gadolinium) must have measurable contrast enhancing disease unless CSF cytology is positive

PATIENT CHARACTERISTICS:

  • Karnofsky performance score 50-100%
  • HIV negative
  • Creatinine clearance ≥ 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No concurrent salicylates, nonsteroidal anti-inflammatory drugs, sulfonamides, or penicillins within the past week
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00416819

Sponsors and Collaborators
University of California, San Francisco
National Cancer Institute (NCI)
Investigators
Study Chair: James L. Rubenstein, MD, PhD University of California, San Francisco
  More Information

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

Publications:

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00416819     History of Changes
Other Study ID Numbers: CDR0000458052, UCSF-03301, UCSF-H9414-23160-02A
Study First Received: December 27, 2006
Last Updated: October 1, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
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
Calcium, Dietary
Cytarabine
Methotrexate
Etoposide phosphate
 Temozolomide
Rituximab
Etoposide
Lenograstim
Leucovorin
Levoleucovorin
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents

ClinicalTrials.gov processed this record on June 18, 2013