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

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ClinicalTrials.gov Identifier: NCT00039130
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : October 22, 2014
Last Update Posted : August 1, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE June 6, 2002
First Posted Date  ICMJE January 27, 2003
Results First Submitted Date  ICMJE October 16, 2014
Results First Posted Date  ICMJE October 22, 2014
Last Update Posted Date August 1, 2016
Study Start Date  ICMJE May 2002
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2014)
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2014)
  • 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 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rituximab, Chemotherapy, and Filgrastim in Treating Patients With Burkitt's Lymphoma or Burkitt's Leukemia
Official Title  ICMJE Phase II Study Of Rituximab And Short Duration, High Intensity Chemotherapy With G-CSF Support In Previously Untreated Patients With Burkitt Lymphoma/Leukemia
Brief 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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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)
Interventions:
  • Biological: filgrastim
  • Biological: rituximab
  • Drug: cyclophosphamide
  • Drug: cytarabine
  • Drug: dexamethasone
  • Drug: doxorubicin hydrochloride
  • Drug: etoposide
  • Drug: ifosfamide
  • Drug: leucovorin calcium
  • Drug: methotrexate
  • Drug: prednisone
  • Drug: vincristine sulfate
  • Drug: Allopurinol
Publications * 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 filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002. Br J Haematol. 2014 Apr;165(1):102-11. doi: 10.1111/bjh.12736. Epub 2014 Jan 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 21, 2011)
105
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00039130
Other Study ID Numbers  ICMJE CALGB-10002
U10CA031946 ( U.S. NIH Grant/Contract )
CALGB-10002
CDR0000069354 ( Registry Identifier: NCI Physician Data Query )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: David Rizzieri, MD Duke University Medical Center Bone Marrow Transplant
PRS Account Alliance for Clinical Trials in Oncology
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP