Clinical trial NCT00098774
Conditions: Lymphoma
Keywords: primary central nervous system non-Hodgkin lymphoma
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2004-10-01; Completion date: 2014-09-01
Enrollment: 47 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

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.

Arms: arm 1: 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)
Interventions: intervention 1: filgrastim intervention 2: rituximab intervention 3: cytarabine intervention 4: etoposide intervention 5: leucovorin calcium intervention 6: methotrexate intervention 7: temozolomide
Intervention descriptions: intervention 1: 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 2: 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 3: 2 g/sq m IV infusion over 2 hours q 12 hrs x 8 doses Days 1-4 of Cycle 6 intervention 4: 5 mg/kg IV infusion over 12 hrs q 12 hrs x 8 doses Days 1-4 of Cycle 6 intervention 5: 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 6: 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 7: 150 mg/sq m PO Days 7-11 Cycles 1-5.

Protocol documents: