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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Cancer and Leukemia Group B.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:
NCT00098774
First received: December 8, 2004
Last updated: June 21, 2011
Last verified: June 2011
  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 with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well rituximab given with combination chemotherapy works in treating patients with newly diagnosed primary CNS lymphoma.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: cytarabine
Drug: etoposide
Drug: leucovorin calcium
Drug: methotrexate
Drug: temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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

Resource links provided by NLM:


Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:
  • Response after remission induction [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relapse-free survival [ Time Frame: After CR until relapse or progression ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: When the first 6, 10, 20, 30 or 45 pts have tox data ] [ Designated as safety issue: Yes ]
  • Neurologic function [ Time Frame: diagnosis, 1, 4, 12, & 36 mon post Tx initiation ] [ Designated as safety issue: No ]
  • Overall Survival & molecular markers [ Time Frame: 2 years and 4 years ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: October 2004
Estimated Study Completion Date: November 2012
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intensive Combination Chemo & Immunotherapy
Standard cancer therapies in investigational combination for treatment of newly diagnosed primary CNS lymphoma.
Biological: filgrastim
5 mcg/kg subQ injection daily Day 14 until ANC > or = 500 uL for 2 days or 1500 uL for 1 day (Cycle 6)
Other Name: G-CSF
Biological: rituximab
375 mg/sq m IV infusion (max rate of 400 mg/hr) on Days 3, 10, 17, & 24 of Cycle 1 nad Days 3 & 10 of Cycle 2
Drug: cytarabine
2 g/sq m IV infusion over 2 hours q 12 hrs x 8 doses Days 1-4 of Cycle 6
Drug: etoposide
5 mg/kg IV infusion over 12 hrs q 12 hrs x 8 doses Days 1-4 of Cycle 6
Drug: leucovorin calcium
100 mg/sq m IV infusion q 6 hrs starting 24 hrs after ea MTX dose until serum MTX < or = 0.05uM Cycles 1-5.
Drug: methotrexate
8 g/sq m IV infusion over 4 hrs Days 1 & 15 Cycles 1, 2, & 3; Day 15 Cycle 4 and Day 1 Cycle 5.
Drug: temozolomide
150 mg/sq m PO Days 7-11 Cycles 1-5.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the complete response rate after remission induction therapy with the combination of high-dose methotrexate (HDMTX), temozolomide, and rituximab at 4 months.

Secondary

  • Determine the safety and feasibility of consolidation therapy comprising cytarabine and etoposide administered after induction therapy in these patients.
  • Determine the percentage of patients who achieve durable (complete and partial) remission when treated with this regimen.
  • Determine relapse-free survival after complete response in patients treated with this regimen.
  • Correlate molecular markers with outcome in patients treated with this regimen.
  • Determine the effects of this regimen on neurological function in these patients.

OUTLINE: This is a multicenter study.

  • Induction Chemotherapy: All induction therapy courses repeat every 28 days.

    • Courses 1-3: Patients receive high-dose methotrexate IV over 4 hours on days 1 and 15, leucovorin calcium IV or orally every 6 hours beginning on days 2 and 16 and continuing until blood levels of methotrexate are in a safe range, and oral temozolomide on days 7-11. Patients also receive rituximab* IV on days 3, 10, 17, and 24 of course 1 and days 3 and 10 of course 2 (total of 6 doses).

NOTE: *Patients diagnosed with T-cell primary CNS lymphoma do not receive rituximab.

  • Course 4: Patients receive oral temozolomide on days 7-11, high-dose methotrexate IV over 4 hours on day 15, and leucovorin calcium IV or orally every 6 hours beginning on day 16 and continuing until blood levels of methotrexate are in a safe range. Patients achieving a complete response or a complete response unconfirmed proceed to consolidation therapy.

    • Consolidation therapy I (course 5): Beginning 4 weeks after the start of course 4, patients receive high-dose methotrexate IV over 4 hours on day 1, leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until blood levels of methotrexate are in a safe range, and oral temozolomide on days 7-11.
    • Consolidation therapy II (course 6): Beginning 3-5 weeks after the start of course 5, patients receive cytarabine IV over 2 hours twice daily and etoposide IV over 12 hours twice daily on days 1-4 and filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning on day 14 and continuing until blood counts recover.

Treatment continues in the absence of disease progression.

After completion of study treatment, patients are followed periodically for 3 years.

PROJECTED ACCRUAL: A total of 27-45 patients will be accrued for this study within 2-3 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed newly diagnosed primary CNS lymphoma confirmed by 1 of the following methods:

    • Brain biopsy or resection
    • Cerebrospinal fluid (CSF) cytology

      • Positive CSF cytology with or without measurable intracranial disease
  • No evidence of systemic non-Hodgkin's lymphoma

    • CT scan or MRI of the chest, abdomen, and pelvis AND bilateral bone marrow biopsy or unilateral biopsy with a 2cm core biopsy specimen that is negative for extracerebral source of lymphoma
  • Measurable contrast-enhancing disease by MRI of the brain and spine (plus gadolinium) unless CSF cytology positive
  • No evidence of pleural effusions or ascites

PATIENT CHARACTERISTICS:

Age

  • Any age

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

  • ALT and AST ≤ 2 times upper limit of normal
  • Bilirubin ≤ 2 mg/dL

Renal

  • Creatinine clearance ≥ 50 mL/min

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 6 months after study participation
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • Not specified

Endocrine therapy

  • Concurrent steroids for the management of symptoms related to lymphoma allowed

Radiotherapy

  • No concurrent palliative radiotherapy

Surgery

  • Not specified
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00098774

  Hide Study Locations
Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Delaware
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Indiana
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States, 46845
United States, Iowa
Hematology Oncology Associates of the Quad Cities
Bettendorf, Iowa, United States, 52722
United States, Kansas
Menorah Medical Center
Overland Park, Kansas, United States, 66209
Saint Luke's Hospital - South
Overland Park, Kansas, United States, 66213
Shawnee Mission Medical Center
Shawnee Mission, Kansas, United States, 66204
United States, Maryland
Union Hospital Cancer Program at Union Hospital
Elkton MD, Maryland, United States, 21921
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Research Medical Center
Kansas City, Missouri, United States, 64132
Parvin Radiation Oncology
Kansas City, Missouri, United States, 64116
North Kansas City Hospital
Kansas City, Missouri, United States, 64116
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
Truman Medical Center - Hospital Hill
Kansas City, Missouri, United States, 64108
St. Joseph Medical Center
Kansas City, Missouri, United States, 64114
Saint Luke's Cancer Institute at Saint Luke's Hospital
Kansas City, Missouri, United States, 64111
Saint Luke's East - Lee's Summit
Lee's Summit, Missouri, United States, 64086
Liberty Hospital
Liberty, Missouri, United States, 64068
Heartland Regional Medical Center
Saint Joseph, Missouri, United States, 64506
United States, New Jersey
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
United States, New York
Stony Brook University Cancer Center
Stony Brook, New York, United States, 11794-9446
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210-1240
United States, Rhode Island
Miriam Hospital
Providence, Rhode Island, United States, 02906
Rhode Island Hospital Comprehensive Cancer Center
Providence, Rhode Island, United States, 02903
United States, Vermont
Mountainview Medical
Berlin, Vermont, United States, 05602
Fletcher Allen Health Care - University Health Center Campus
Burlington, Vermont, United States, 05401
United States, Virginia
Danville Regional Medical Center
Danville, Virginia, United States, 24541
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: James L. Rubenstein, MD, PhD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00098774     History of Changes
Other Study ID Numbers: CDR0000398106, U10CA031946, CALGB-50202
Study First Received: December 8, 2004
Last Updated: June 21, 2011
Health Authority: United States: Federal Government

Keywords provided by Cancer and Leukemia Group B:
primary central nervous system non-Hodgkin lymphoma

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Methotrexate
Temozolomide
Rituximab
Etoposide
Lenograstim
Leucovorin
Levoleucovorin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on April 22, 2014