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

August 16, 2023 updated by: Alliance for Clinical Trials in Oncology

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

105

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92134
        • Naval Medical Center - San Diego
    • Delaware
      • Lewes, Delaware, United States, 19958
        • Tunnell Cancer Center at Beebe Medical Center
      • Newark, Delaware, United States, 19713
        • CCOP - Christiana Care Health Services
    • District of Columbia
      • Washington, District of Columbia, United States, 20307-5001
        • Walter Reed Army Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637-1470
        • University of Chicago Cancer Research Center
      • Chicago, Illinois, United States, 60612-7243
        • University of Illinois Cancer Center
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Fort Wayne Medical Oncology and Hematology
    • Iowa
      • Bettendorf, Iowa, United States, 52722
        • Hematology Oncology Associates of the Quad Cities
      • Iowa City, Iowa, United States, 52242-1002
        • Holden Comprehensive Cancer Center at University of Iowa
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Greenebaum Cancer Center at University of Maryland Medical Center
      • Elkton, Maryland, United States, 21921
        • Union Hospital Cancer Program at Union Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center at University of Minnesota
    • Missouri
      • Columbia, Missouri, United States, 65203
        • Ellis Fischel Cancer Center at University of Missouri - Columbia
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756-0002
        • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
    • New Jersey
      • Voorhees, New Jersey, United States, 08043
        • Cancer Institute of New Jersey at Cooper - Voorhees
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • Lake Success, New York, United States, 11042
        • Monter Cancer Center of the North Shore-LIJ Health System
      • Manhasset, New York, United States, 11030
        • CCOP - North Shore University Hospital
      • Manhasset, New York, United States, 11030
        • Don Monti Comprehensive Cancer Center at North Shore University Hospital
      • New Hyde Park, New York, United States, 11040
        • Long Island Jewish Medical Center
      • Stony Brook, New York, United States, 11794-9446
        • Stony Brook University Cancer Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28233-3549
        • Presbyterian Cancer Center at Presbyterian Hospital
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
      • Goldsboro, North Carolina, United States, 27534
        • Wayne Memorial Hospital, Incorporated
      • Winston-Salem, North Carolina, United States, 27157-1096
        • Wake Forest University Comprehensive Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210-1240
        • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Miriam Hospital
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital Comprehensive Cancer Center
    • Vermont
      • Berlin, Vermont, United States, 05602
        • Mountainview Medical
      • Burlington, Vermont, United States, 05401
        • Fletcher Allen Health Care - University Health Center Campus
    • Virginia
      • Richmond, Virginia, United States, 23298-0037
        • Virginia Commonwealth University Massey Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab with High Intensity Chemotherapy
Cycle1: Cyclophosphamide 100 mg/m^2/day (d) IV (d 1-5), Prednisone 60 mg/m^2/d oral (d 1-7), Allopurinal 300 mg/d oral (d 1-14) Cycle 2, 4 & 6 (21 day): Ifosfamide 800 mg/m^2/d (d 1-5), Dexamethasone 10 mg/m^2/d (d1-5), Methotrexate 150 mg/m^2 load, then 1.35 g/m^2 over 23.5 h (d 1), Leucovorin 25 mg/m^2 36 h after methotrexate (d 2) then 10 mg/m^2 every 6 h, Vincristine 2 mg push (d 1), Cytarabine 1000 mg/m^2/d over 2 h (d 4-5), Etoposide 80 mg/m^2.d over 1 h (d 4-5), Filgrastim 5 mg/kg/d (d 7-21 as needed), Rituximab 50 mg/m^2 d 8 cycle 2 only, 375 mg/m^2/d (d 10, 12 cycle 2, d 8 cycle 4 & 6) Cycle 3, 5 & 7 (21 day): Cyclophosphamide 200 mg/m^2/day (d) IV (d 1-5), Dexamethasone 10 mg/m^2/d (d1-5), Methotrexate 150 mg/m^2 load, then 1.35 g/m^2 over 23.5 h (d 1), Leucovorin 50 mg/m^2 36 h after methotrexate (d 2) then 10 mg/m^2 every 6 h, Vincristine 2 mg push (d 1), Doxorubicin 25 mg/m^2/d (d 4-5), Filgrastim 5 mg/kg/d (d 7-21 as needed), Rituximab 375 mg/m^2/d (d 8)
Biological: filgrastim
5 ug/kg/day sub Q injection day 7 until ANC>5000/ul courses II-VII
Biological: 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
Drug: cytarabine
1 g/sq m/day IV infusion Days 4 & 5, courses II, IV, VI
Drug: dexamethasone
10mg/sq m PO or IV Days 1-5 courses II-VII
Drug: doxorubicin hydrochloride
25 mg/sq m/day IV infusion Days 4 & 5 courses III,V, VII
Drug: etoposide
80 mg/sq m/day IV infusion Days 4 & 5 courses II, IV, VI
Drug: ifosfamide
800 mg/sq m/day IV infusion Days 1-5 courses II, IV, VI
Drug: leucovorin calcium
25mg/sq m IV infusion over 15 min then 10 mg IV q 6 hrs until serum MTX <10nM, courses II-VII
Drug: methotrexate
1.5 g/sq m IV infusion Day 1 courses II-VII
Drug: prednisone
60 mg/sq m PO/day Days 1-7 course I
Drug: vincristine sulfate
2 mg IV push Day 1 courses II-VII
Drug: Allopurinol
300 mg/day PO Days 1-14, course I

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response Rate
Time Frame: 6 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
2 Year Event Free Survival
Time Frame: 2 years
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
2 Year Overall Survival
Time Frame: 2 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: David Rizzieri, MD, Duke University Medical Center Bone Marrow Transplant

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2002

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

June 6, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimated)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

August 21, 2023

Last Update Submitted That Met QC Criteria

August 16, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CALGB-10002
  • U10CA031946 (U.S. NIH Grant/Contract)
  • CDR0000069354 (Registry Identifier: NCI Physician Data Query)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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