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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00039130
First received: June 6, 2002
Last updated: November 23, 2015
Last verified: November 2015
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
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
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Complete Response Rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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:
  • 2 Year Event Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Percentage of participants who were alive at 2 years. The 2 year survival, with 95% confidence interval, was estimated using the Kaplan Meier method.


Enrollment: 105
Study Start Date: May 2002
Study Completion Date: October 2014
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00039130

  Show 31 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: David Rizzieri, MD Duke University Medical Center Bone Marrow Transplant
  More Information

Publications:
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00039130     History of Changes
Other Study ID Numbers: CALGB-10002  U10CA031946  CDR0000069354 
Study First Received: June 6, 2002
Results First Received: October 16, 2014
Last Updated: November 23, 2015
Health Authority: United States: Federal Government

Keywords provided by Alliance for Clinical Trials in Oncology:
untreated adult acute lymphoblastic leukemia
L3 adult acute lymphoblastic leukemia
stage I adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult Burkitt lymphoma

Additional relevant MeSH terms:
Lymphoma
Leukemia
Burkitt Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Dexamethasone acetate
Dexamethasone
Prednisone
Dexamethasone 21-phosphate
Liposomal doxorubicin
Etoposide phosphate
Isophosphamide mustard
Cyclophosphamide
Rituximab
Methotrexate
Doxorubicin
Etoposide
Cytarabine
Vincristine

ClinicalTrials.gov processed this record on July 21, 2016