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

NCT ID: NCT00068250

Last Updated: 2018-02-07

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-07-31

Study Completion Date

2016-12-31

Brief Summary

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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.

Detailed Description

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OBJECTIVES:

* To assess the maximum tolerated dose (MTD) of temozolomide (TMZ) in combination with methotrexate (MTX) and rituximab (RTX) when administered prior to twice daily fractionated whole brain radiation therapy (WBRT) in patients with primary central nervous system lymphoma.
* To compare the two-year survival rate in patients receiving pre-irradiation chemotherapy, twice daily fractionated whole brain radiation therapy and post-irradiation temozolomide to the reported two-year survival rate of Radiation Therapy Oncology Group (RTOG) trial 93-10. RTOG 9310 does not fall within ClinicalTrials.gov registration/reporting requirements.)
* To compare the pre-irradiation chemotherapy tumor response rates to the reported rate from RTOG 93-10.
* To report progression-free survival.
* To assess acute and long-term neurologic toxicity, and to collect quality of life data for this patient group.

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

Conditions

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Brain and Central Nervous System Tumors Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase I: Temozolomide 100 mg

Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.

Group Type EXPERIMENTAL

rituximab

Intervention Type DRUG

375 mg/m2, intravenously three days prior to the first cycle of methotrexate

methotrexate

Intervention Type DRUG

Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.

temozolomide 100 mg/m^2

Intervention Type DRUG

Temozolomide 100 mg/m\^2 by mouth per day for five days on weeks 4 and 8.

radiation therapy

Intervention Type RADIATION

Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.

post-radiation therapy temozolomide

Intervention Type DRUG

Temozolomide (TMZ) 200 mg/m\^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.

Phase I: Temozolomide 150 mg

Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.

Group Type EXPERIMENTAL

rituximab

Intervention Type DRUG

375 mg/m2, intravenously three days prior to the first cycle of methotrexate

methotrexate

Intervention Type DRUG

Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.

temozolomide 150 mg/m^2

Intervention Type DRUG

Temozolomide 150 mg/m\^2 by mouth per day for five days on weeks 4 and 8.

radiation therapy

Intervention Type RADIATION

Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.

post-radiation therapy temozolomide

Intervention Type DRUG

Temozolomide (TMZ) 200 mg/m\^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.

Phase I: Temozolomide 200 mg

Rituximab, methotrexate, temozolomide 200 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.

Group Type EXPERIMENTAL

rituximab

Intervention Type DRUG

375 mg/m2, intravenously three days prior to the first cycle of methotrexate

methotrexate

Intervention Type DRUG

Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.

temozolomide 200 mg/m^2

Intervention Type DRUG

Temozolomide 200 mg/m\^2 per day by mouth for five days on weeks 4 and 8.

radiation therapy

Intervention Type RADIATION

Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.

post-radiation therapy temozolomide

Intervention Type DRUG

Temozolomide (TMZ) 200 mg/m\^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.

Phase II: Temozolomide 100 mg

Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.

Group Type EXPERIMENTAL

rituximab

Intervention Type DRUG

375 mg/m2, intravenously three days prior to the first cycle of methotrexate

methotrexate

Intervention Type DRUG

Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.

temozolomide 100 mg/m^2

Intervention Type DRUG

Temozolomide 100 mg/m\^2 by mouth per day for five days on weeks 4 and 8.

radiation therapy

Intervention Type RADIATION

Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.

post-radiation therapy temozolomide

Intervention Type DRUG

Temozolomide (TMZ) 200 mg/m\^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.

Interventions

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rituximab

375 mg/m2, intravenously three days prior to the first cycle of methotrexate

Intervention Type DRUG

methotrexate

Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.

Intervention Type DRUG

temozolomide 100 mg/m^2

Temozolomide 100 mg/m\^2 by mouth per day for five days on weeks 4 and 8.

Intervention Type DRUG

temozolomide 150 mg/m^2

Temozolomide 150 mg/m\^2 by mouth per day for five days on weeks 4 and 8.

Intervention Type DRUG

temozolomide 200 mg/m^2

Temozolomide 200 mg/m\^2 per day by mouth for five days on weeks 4 and 8.

Intervention Type DRUG

radiation therapy

Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.

Intervention Type RADIATION

post-radiation therapy temozolomide

Temozolomide (TMZ) 200 mg/m\^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.

Intervention Type DRUG

Other Intervention Names

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radiotherapy

Eligibility Criteria

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Inclusion Criteria

1. Primary central nervous system (CNS) lymphoma \[B-cell, Cluster of Differentiation 20 (CD20) antigen positive\] based on positive biopsy or cerebrospinal fluid (CSF) or vitreous cytology (in association with measurable intraparenchymal tumor). Cytology must demonstrate lymphoma or have an immunohistochemical diagnosis of malignant lymphocytes with a monoclonal lymphocytic population.
2. Life expectancy ≥ 8 weeks;
3. Zubrod performance status of 0-2;
4. Absolute granulocyte count ≥1500/mm3; platelet count ≥ 100,000/mm3; creatinine clearance ≥ 50, calculated with the Cockcroft-Gault Equation: Cr Clearance = (140-age) x wt (kg)/(Cr\[mg/dl\]x 72); Bilirubin, serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (AST) ≤ 2 x institutional upper limits of normal;
5. Patients must sign a study-specific informed consent prior to study entry.
6. Age ≥ 18

Exclusion Criteria

1. Evidence of systemic lymphoma;
2. Prior malignancy (excluding in situ carcinoma of the cervix or non-melanomatous skin cancer)unless disease free for at least five years;
3. Prior radiotherapy to the brain or head/neck;
4. Prior chemotherapy;
5. History of idiopathic sensitivity to any of the drugs to be used;
6. Active infectious process;
7. Seropositive for HIV, AIDS, or post-organ transplant;
8. Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus.
9. Active hepatitis B.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

NRG Oncology

OTHER

Sponsor Role collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jon Glass, MD

Role: STUDY_CHAIR

Sidney Kimmel Cancer Center at Thomas Jefferson University

Locations

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Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, United States

Site Status

Integrated Community Oncology Network at Southside Cancer Center

Jacksonville, Florida, United States

Site Status

Baptist Medical Center South

Jacksonville, Florida, United States

Site Status

Integrated Community Oncology Network

Jacksonville Beach, Florida, United States

Site Status

Integrated Community Oncology Network - Orange Park

Orange Park, Florida, United States

Site Status

Florida Cancer Center - Palatka

Palatka, Florida, United States

Site Status

Flagler Cancer Center

Saint Augustine, Florida, United States

Site Status

Borgess Medical Center

Kalamazoo, Michigan, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Site Status

CCOP - Kansas City

Kansas City, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

John F. Kennedy Medical Center

Edison, New Jersey, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Providence Milwaukie Hospital

Milwaukie, Oregon, United States

Site Status

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, United States

Site Status

CCOP - Columbia River Oncology Program

Portland, Oregon, United States

Site Status

Providence St. Vincent Medical Center

Portland, Oregon, United States

Site Status

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, United States

Site Status

Utah Valley Regional Medical Center - Provo

Provo, Utah, United States

Site Status

Southwest Washington Medical Center Cancer Center

Vancouver, Washington, United States

Site Status

Community Memorial Hospital Cancer Care Center

Menomonee Falls, Wisconsin, United States

Site Status

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Glass J, Won M, Schultz CJ, Brat D, Bartlett NL, Suh JH, Werner-Wasik M, Fisher BJ, Liepman MK, Augspurger M, Bokstein F, Bovi JA, Solhjem MC, Mehta MP. Phase I and II Study of Induction Chemotherapy With Methotrexate, Rituximab, and Temozolomide, Followed By Whole-Brain Radiotherapy and Postirradiation Temozolomide for Primary CNS Lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016 May 10;34(14):1620-5. doi: 10.1200/JCO.2015.64.8634. Epub 2016 Mar 28.

Reference Type RESULT
PMID: 27022122 (View on PubMed)

Other Identifiers

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CDR0000301563

Identifier Type: -

Identifier Source: secondary_id

RTOG-0227

Identifier Type: -

Identifier Source: org_study_id

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