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

Lymphoma Clinical Trial

Official title:

Intensive Chemotherapy And Immunotherapy In Patients With Newly Diagnosed Primary CNS Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00098774
• Other study ID #: CALGB-50202
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 2
• First received: December 8, 2004
• Last updated: July 1, 2016
• Start date: October 2004
• Est. completion date: September 2014

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: September 2014
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• 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)
• 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

Drug:
• cytarabine
2 g/sq m IV infusion over 2 hours q 12 hrs x 8 doses Days 1-4 of Cycle 6
• etoposide
5 mg/kg IV infusion over 12 hrs q 12 hrs x 8 doses Days 1-4 of Cycle 6
• 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.
• 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.
• temozolomide
150 mg/sq m PO Days 7-11 Cycles 1-5.

Locations

Country	Name	City	State
United States	Mountainview Medical	Berlin	Vermont
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Union Hospital Cancer Program at Union Hospital	Elkton MD	Maryland
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	CCOP - Kansas City	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Parvin Radiation Oncology	Kansas City	Missouri
United States	Research Medical Center	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	Truman Medical Center - Hospital Hill	Kansas City	Missouri
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Liberty Hospital	Liberty	Missouri
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's Hospital - South	Overland Park	Kansas
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Rubenstein JL, Hsi ED, Johnson JL, Jung SH, Nakashima MO, Grant B, Cheson BD, Kaplan LD. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol. 2013 Sep 1;31(25):3061-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate After Remission Induction	Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Complete response requires disappearance of all evidence of disease.	4 months	No
Secondary	4 Year Progression Free Rate	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 body	4 years	No
Secondary	Change From Baseline in Mini-Mental Status Evaluation at 4 Months	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.	Baseline & month 4	No
Secondary	4 Year Overall Survival Rate	Percentage of patients who were alive at 4 years. The 4-year survival rate was estimated using the Kaplan Meier method.	4 years	No