Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Primary CNS Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: filgrastimBiological: rituximab
- Registration Number
- NCT00098774
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 47
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Intensive Combination Chemo & Immunotherapy filgrastim 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) Intensive Combination Chemo & Immunotherapy rituximab 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) Intensive Combination Chemo & Immunotherapy leucovorin calcium 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) Intensive Combination Chemo & Immunotherapy etoposide 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) Intensive Combination Chemo & Immunotherapy cytarabine 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) Intensive Combination Chemo & Immunotherapy methotrexate 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) Intensive Combination Chemo & Immunotherapy temozolomide 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)
- Primary Outcome Measures
Name Time Method Complete Response Rate After Remission Induction 4 months Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Complete response requires disappearance of all evidence of disease.
- Secondary Outcome Measures
Name Time Method 4 Year Progression Free Rate 4 years Percentage of patients who were progression free at 4 years. The 4-year progression free rate was estimated using the Kaplan Meier method.
Relapse was assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Progression required a 25% increase of previous area of gadolinium enhancement, appearance of new areas of T1 gadolinium enhancement or new appearance of malignant cells in the spinal fluid or new tumor appearance in other sites of the body4 Year Overall Survival Rate 4 years Percentage of patients who were alive at 4 years. The 4-year survival rate was estimated using the Kaplan Meier method.
Change From Baseline in Mini-Mental Status Evaluation at 4 Months Baseline & month 4 Neurologic functioning will be assessed using the Mini-Mental Status Evaluation (MMSE), a standardized, bedside tool for evaluation of higher mental function. This assessment is based on a 30-point scale (0-30) with higher scores associated with better performance.
Trial Locations
- Locations (30)
Saint Luke's Hospital - South
🇺🇸Overland Park, Kansas, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸Voorhees, New Jersey, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Masonic Cancer Center at University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Danville Regional Medical Center
🇺🇸Danville, Virginia, United States
Fort Wayne Medical Oncology and Hematology
🇺🇸Fort Wayne, Indiana, United States
CCOP - Kansas City
🇺🇸Kansas City, Missouri, United States
Rhode Island Hospital Comprehensive Cancer Center
🇺🇸Providence, Rhode Island, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Hematology Oncology Associates of the Quad Cities
🇺🇸Bettendorf, Iowa, United States
Menorah Medical Center
🇺🇸Overland Park, Kansas, United States
Union Hospital Cancer Program at Union Hospital
🇺🇸Elkton MD, Maryland, United States
Shawnee Mission Medical Center
🇺🇸Shawnee Mission, Kansas, United States
Truman Medical Center - Hospital Hill
🇺🇸Kansas City, Missouri, United States
North Kansas City Hospital
🇺🇸Kansas City, Missouri, United States
Saint Luke's Cancer Institute at Saint Luke's Hospital
🇺🇸Kansas City, Missouri, United States
St. Joseph Medical Center
🇺🇸Kansas City, Missouri, United States
Parvin Radiation Oncology
🇺🇸Kansas City, Missouri, United States
Liberty Hospital
🇺🇸Liberty, Missouri, United States
Stony Brook University Cancer Center
🇺🇸Stony Brook, New York, United States
Saint Luke's East - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Mountainview Medical
🇺🇸Berlin, Vermont, United States
Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Fletcher Allen Health Care - University Health Center Campus
🇺🇸Burlington, Vermont, United States