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Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For Primary Central Nervous System Lymphoma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Brain and Central Nervous System Tumors, Lymphoma

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Trial Information

Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For 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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity rate (Phase I)

Outcome Time Frame:

From start of treatment to 10 weeks.

Safety Issue:

Yes

Principal Investigator

Jon Glass, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Kimmel Cancer Center (KCC)

Authority:

United States: Federal Government

Study ID:

RTOG-0227

NCT ID:

NCT00068250

Start Date:

July 2003

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Lymphoma
  • primary central nervous system non-Hodgkin lymphoma
  • primary central nervous system Hodgkin lymphoma
  • Lymphoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location

CCOP - Kansas CityKansas City, Missouri  64131
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
John F. Kennedy Medical CenterEdison, New Jersey  08818
CCOP - Columbia River Oncology ProgramPortland, Oregon  97225
Kimmel Cancer Center at Thomas Jefferson University - PhiladelphiaPhiladelphia, Pennsylvania  19107
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Utah Valley Regional Medical Center - ProvoProvo, Utah  84604
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Baptist Cancer Institute - JacksonvilleJacksonville, Florida  32207
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
CCOP - Nevada Cancer Research FoundationLas Vegas, Nevada  89109-2306
Providence Milwaukie HospitalMilwaukie, Oregon  97222
Providence Cancer Center at Providence Portland Medical CenterPortland, Oregon  97213-2967
Providence St. Vincent Medical CenterPortland, Oregon  97225
Southwest Washington Medical Center Cancer CenterVancouver, Washington  98668
Jon and Karen Huntsman Cancer Center at Intermountain Medical CenterMurray, Utah  84157
Community Memorial Hospital Cancer Care CenterMenomonee Falls, Wisconsin  53051
Integrated Community Oncology NetworkJacksonville Beach, Florida  32250
Baptist Medical Center SouthJascksonville, Florida  32258
Florida Cancer Center - PalatkaPalatka, Florida  32177
Flagler Cancer CenterSaint Augustine, Florida  32086
Integrated Community Oncology Network - Orange ParkOrange Park, Florida  32073
Integrated Community Oncology Network at Southside Cancer CenterJacksonville, Florida  32207