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

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-10-31

Study Completion Date

2014-09-30

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intensive Combination Chemo & Immunotherapy

Induction Cycles 1-3: Methotrexate 8gm/m\^2 days 1 \& 15; Leucovorin 100 mg/m\^2 days 2 \& 16; Rituximab 375 mg/m\^2 days 3, 10, 17 \& 24 of cycle 1, days 3 \& 10 of cycle 2; Temozolomide 150 mg/m\^2/day PO days 7-11

Induction Cycle 4: Temozolomide 150 mg/m\^2/day PO days 7-11; Methotrexate 8gm/m\^2 day 15; Leucovorin 100 mg/m\^2 day 16

Consolidation Cycle 5: Methotrexate 8gm/m\^2 days 1; Leucovorin 100 mg/m\^2 days 2; Temozolomide 150 mg/m\^2/day PO days 7-11

Consolidation Cycle 6: Cytarabine 2 g/m\^2 (x 8 doses) days 1-4; Etoposide 5 mg/kg (x 8 doses) days 1-4; G-CSF 5 mcg/kg/day or GM-CSF 250 mcg/m\^2/day starting day 14 until ANC recovers (\>= 500 for 2 consecutive days or \>= 1500 for one day)

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

5 mcg/kg subQ injection daily Day 14 until ANC \> or = 500 uL for 2 days or 1500 uL for 1 day (Cycle 6)

rituximab

Intervention Type BIOLOGICAL

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

cytarabine

Intervention Type DRUG

2 g/sq m IV infusion over 2 hours q 12 hrs x 8 doses Days 1-4 of Cycle 6

etoposide

Intervention Type DRUG

5 mg/kg IV infusion over 12 hrs q 12 hrs x 8 doses Days 1-4 of Cycle 6

leucovorin calcium

Intervention Type DRUG

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.

methotrexate

Intervention Type DRUG

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.

temozolomide

Intervention Type DRUG

150 mg/sq m PO Days 7-11 Cycles 1-5.

Interventions

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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)

Intervention Type 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

Intervention Type BIOLOGICAL

cytarabine

2 g/sq m IV infusion over 2 hours q 12 hrs x 8 doses Days 1-4 of Cycle 6

Intervention Type DRUG

etoposide

5 mg/kg IV infusion over 12 hrs q 12 hrs x 8 doses Days 1-4 of Cycle 6

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

temozolomide

150 mg/sq m PO Days 7-11 Cycles 1-5.

Intervention Type DRUG

Other Intervention Names

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G-CSF

Eligibility Criteria

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Inclusion 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

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James Rubenstein, MD, PhD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

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UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

Site Status

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

Site Status

Hematology Oncology Associates of the Quad Cities

Bettendorf, Iowa, United States

Site Status

Menorah Medical Center

Overland Park, Kansas, United States

Site Status

Saint Luke's Hospital - South

Overland Park, Kansas, United States

Site Status

Shawnee Mission Medical Center

Shawnee Mission, Kansas, United States

Site Status

Union Hospital Cancer Program at Union Hospital

Elkton MD, Maryland, United States

Site Status