Rituximab, Chemotherapy, and Filgrastim in Treating Patients With Burkitt's Lymphoma or Burkitt's Leukemia

Lymphoma Clinical Trial

Official title:

Phase II Study Of Rituximab And Short Duration, High Intensity Chemotherapy With G-CSF Support In Previously Untreated Patients With Burkitt Lymphoma/Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00039130
• Other study ID #: CALGB-10002
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 2
• Start date: May 2002
• Est. completion date: October 2014

Study information

• Verified date: August 2023
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the numbers of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Combining chemotherapy with rituximab and filgrastim may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with chemotherapy and filgrastim in treating patients who have Burkitt's lymphoma or Burkitt's leukemia.

Description:

OBJECTIVES:

• Determine the complete response rate in patients with previously untreated Burkitt's lymphoma or Burkitt's leukemia treated with rituximab and high-intensity chemotherapy with filgrastim (G-CSF) support.

• Determine the progression-free and overall survival of patients treated with this regimen.

• Determine the feasibility and toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (leukemia vs lymphoma).

• Course 1: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5 and oral prednisone on days 1-7. Allopurinol PO will be given on days 1-14.

• Courses 2, 4, and 6: Patients receive ifosfamide IV over 1 hour daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV over 15 minutes every 6 hours on day 2; cytarabine IV over 2 hours on days 4 and 5 and etoposide IV over 1 hour daily on days 4 and 5; oral dexamethasone daily on days 1-5; and methotrexate and cytarabine intrathecally (IT) on day 1. During course 2, patients receive rituximab IV over 1-4 hours on days 8, 10, and 12. During courses 4 and 6, patients receive rituximab IV over 1 hour on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 7 and continuing until blood counts recover.

• Courses 3, 5, and 7: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV every 6 hours on day 2; doxorubicin IV daily on days 4 and 5; oral dexamethasone daily on days 1-5; methotrexate and cytarabine IT on day 1; and rituximab IV over 1 hour on day 8. Patients also receive G-CSF as in courses 2, 4, and 6. After course 3, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per stratum) will be accrued for this study within 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: October 2014
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically, cytogenetically, or immunophenotypically confirmed Burkitt's leukemia or Burkitt's or Burkitt-like lymphoma

• L3 morphology surface IgG expression

• Cytogenetic evidence for t(8;14), t(8;22), or t(2;8)

• Previously untreated disease except hydroxyurea for leukocytosis

• CNS involvement allowed

• Patients with Burkitt's leukemia or Burkitt's lymphoma with bone marrow involvement must also be enrolled on CALGB-8461

• Patients with Burkitt's leukemia must also be enrolled on CALGB-9665

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)

Renal:

• Creatinine no greater than 1.5 times ULN

Other:

• HIV negative

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent interleukin-11

Chemotherapy:

• See Disease Characteristics

• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except for non-disease-related conditions (e.g., insulin for diabetes)

• No concurrent steroids except for adrenal failure

Radiotherapy:

• No concurrent palliative radiotherapy except whole-brain irradiation for documented CNS disease

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Leukemia
• Lymphoma

Intervention

Biological:
• filgrastim
5 ug/kg/day sub Q injection day 7 until ANC>5000/ul courses II-VII
• rituximab
Day 8 course II 50 mg/sq m IV infusion: d 8 course IV & VI 375mg/sq m IV Day 10 course II: 325 mg/sq m IV infusion Day 12 course II: 375 mg/sq m IV infusion

Drug:
• cyclophosphamide
200 mg/sq m/day IV infusion over 5-15 min days 1-5, courses I, III, V, VII
• cytarabine
1 g/sq m/day IV infusion Days 4 & 5, courses II, IV, VI
• dexamethasone
10mg/sq m PO or IV Days 1-5 courses II-VII
• doxorubicin hydrochloride
25 mg/sq m/day IV infusion Days 4 & 5 courses III,V, VII
• etoposide
80 mg/sq m/day IV infusion Days 4 & 5 courses II, IV, VI
• ifosfamide
800 mg/sq m/day IV infusion Days 1-5 courses II, IV, VI
• leucovorin calcium
25mg/sq m IV infusion over 15 min then 10 mg IV q 6 hrs until serum MTX <10nM, courses II-VII
• methotrexate
1.5 g/sq m IV infusion Day 1 courses II-VII
• prednisone
60 mg/sq m PO/day Days 1-7 course I
• vincristine sulfate
2 mg IV push Day 1 courses II-VII
• Allopurinol
300 mg/day PO Days 1-14, course I

Locations

Country	Name	City	State
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Mountainview Medical	Berlin	Vermont
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Monter Cancer Center of the North Shore-LIJ Health System	Lake Success	New York
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Naval Medical Center - San Diego	San Diego	California
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

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)

Rizzieri DA, Johnson JL, Byrd JC, Lozanski G, Blum KA, Powell BL, Shea TC, Nattam S, Hoke E, Cheson BD, Larson RA; Alliance for Clinical Trials In Oncology (ACTION). Improved efficacy using rituximab and brief duration, high intensity chemotherapy with fi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate	Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Complete response requires disappearance of all evidence of disease.	6 months
Secondary	2 Year Event Free Survival	Percentage of patients who were event free at 2 years. The 2-year event free rate was estimated using the Kaplan Meier method. An event is defined as death, progression or treatment failure.	2 years
Secondary	2 Year Overall Survival	Percentage of participants who were alive at 2 years. The 2 year survival, with 95% confidence interval, was estimated using the Kaplan Meier method.	2 years