Clinical trial NCT00335140
Conditions: Lymphoma
Keywords: primary central nervous system non-Hodgkin lymphoma
Sponsor: Eastern Cooperative Oncology Group
Start date: 2007-08-23; Completion date: 2015-07-01
Enrollment: 26 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as methotrexate, leucovorin, vincristine, procarbazine, dexamethasone, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with primary central nervous system (CNS) lymphoma.

Detailed description:
OBJECTIVES:

Primary

* Determine the complete response rate.

Secondary

* Determine the progression-free survival of these patients.
* Determine the proportion of progression-free and overall survival in these patients.
* Determine rituximab cerebrospinal fluid pharmacokinetics (only in patients requiring intrathecal chemotherapy).

OUTLINE: This is a multicenter study.

Patients receive rituximab IV 3 times weekly in weeks 1-4; high-dose methotrexate IV over 2 hours in weeks 1, 3, 5, and 9; oral or IV leucovorin calcium every 6 hours for 12 doses beginning 24 hours after the start of methotrexate in weeks 1, 3, 5, and 9; vincristine IV in weeks 1, 3, 5, 7, and 9; oral procarbazine hydrochloride daily on days 1-7 in weeks 1, 5, and 9; oral dexamethasone daily in weeks 1-6; and cytarabine IV over 2 hours twice weekly in weeks 11 and 14.

Patients with positive cerebrospinal fluid also receive methotrexate intrathecally and oral leucovorin calcium every 12 hours for 8 doses beginning 24 hours after the start of methotrexate in weeks 2, 4, 6, 8, and 10.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Arms: arm 1: Rituximab + high dose methotrexate, leucovorin, vincristine, procarbazine, dexamethasone, and cytarabine. Patients with meningeal involvement will receive additional methotrexate and leucovorin.
Interventions: intervention 1: Rituximab intervention 2: Cytarabine intervention 3: Dexamethasone intervention 4: Leucovorin intervention 5: Methotrexate intervention 6: Procarbazine intervention 7: Vincristine
Intervention descriptions: intervention 1: Rituximab is administered intravenously. The initial rate is 50 mg/hr for the first hour. If no toxicity is seen, the rate may be escalated gradually in 50 mg/hour increments at 30-minute intervals to a maximum of 300 mg/hr. If the first dose is well tolerated, the initial rate for subsequent dose is 100 mg/hr, increased gradually in 100 mg/hr increments at 30-minute intervals, not to exceed 400 mg/hr. intervention 2: 3 g/m2/day in 500 cc D5W IV over 2 hrs. x 2 doses 24hrs. apart, Weeks 11, 14 intervention 3: 16mg (week 1) PO daily Weeks 1, 2, 3, 4, 5, 6 Taper by 4 mg/wk, weeks 2, 3, by 2 mg/wk week 4, 5, 6 intervention 4: 25 mg PO/IV every 6 hrs. x 12 doses, Weeks 1, 3, 5, 7, 9 For patients with meningeal involvement additionally 10 mg PO every 12 hrs. x 8 doses, Weeks 2, 4, 6, 8, 10 intervention 5: 3.5 g/m2In 500 cc D5W + 25 mEq NaHCO3 IV over 2 hours, Weeks 1, 3, 5, 7, 9

For patients with meningeal involvement additionally:

12 mg Intrathecally, in preservative-free sterile .9NS Weeks 2, 4, 6, 8, 10 Via Ommaya or lumbar puncture intervention 6: 100 mg/m2 PO daily x 7 days Weeks 1, 5, 9 intervention 7: 1.4 mg/m2 IV push, Weeks 1, 3, 5, 7, 9 2m2 (2.8 mg) dose cap

Protocol documents: