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

September 10, 2003
June 21, 2013
July 2003
July 2016   (final data collection date for primary outcome measure)
  • 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 ]
Not Provided
Complete list of historical versions of study NCT00068250 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma
Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For Primary Central Nervous System Lymphoma

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Brain and Central Nervous System Tumors
  • Lymphoma
  • Biological: rituximab
  • Drug: methotrexate
  • Drug: temozolomide
  • Radiation: radiation therapy
  • Experimental: Phase I: Temozolomide (TMZ) 100mg
    Phase I: Temozolomide 100mg
    Interventions:
    • Biological: rituximab
    • Drug: methotrexate
    • Drug: temozolomide
    • Radiation: radiation therapy
  • Experimental: Phase I: Temozolomide (TMZ) 150 mg
    Phase I: Temozolomide 150 mg
    Interventions:
    • Biological: rituximab
    • Drug: methotrexate
    • Drug: temozolomide
    • Radiation: radiation therapy
  • Experimental: Phase I: Temozolomide (TMZ) 200 mg
    Phase I: Temozolomide 200 mg
    Interventions:
    • Biological: rituximab
    • Drug: methotrexate
    • Drug: temozolomide
    • Radiation: radiation therapy
  • Experimental: Phase II: Temozolomide (TMZ) 100 mg
    Phase II: Temozolomide 100 mg
    Interventions:
    • Biological: rituximab
    • Drug: methotrexate
    • Drug: temozolomide
    • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
60
Not Provided
July 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00068250
RTOG-0227, CDR0000301563
Yes
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Study Chair: Jon Glass, MD Kimmel Cancer Center (KCC)
Radiation Therapy Oncology Group
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP