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Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed Burkitt's Lymphoma or Leukemia

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ClinicalTrials.gov Identifier: NCT00133991
Recruitment Status : Completed
First Posted : August 24, 2005
Results First Posted : September 17, 2018
Last Update Posted : September 17, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief 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. Giving more than one drug (combination chemotherapy) may kill more cancer cells. 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 combination chemotherapy together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with newly diagnosed Burkitt's lymphoma or leukemia.


Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Biological: Filgrastim Biological: Rituximab Drug: Cyclophosphamide Drug: Cytarabine Drug: Methotrexate Drug: Prednisone Drug: Hydrocortisone Drug: Vincristine Drug: Leucovorin Phase 2

Detailed Description:

OBJECTIVES:

Primary

  • Determine the overall response rate, 1-year event-free survival, and overall survival of adult patients with newly diagnosed Burkitt or atypical Burkitt lymphoma or leukemia treated with dose-intensified induction therapy comprising cyclophosphamide, vincristine, prednisone, and rituximab followed by consolidation therapy comprising rituximab and high-dose cyclophosphamide.
  • Determine the grade 3 or higher non-hematologic toxic effects and overall tolerability of this regimen in these patients.

Secondary

  • Determine the 3-year event-free survival and overall survival of patients treated with this regimen.
  • Determine the general patterns of CNS and systemic relapse in patients treated with this regimen.

OUTLINE: This is a multicenter study.

  • Dose-intensified CVP induction therapy: Patients receive cyclophosphamide IV and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5 and rituximab IV on days 1 and 8, and high-dose methotrexate IV with leucovorin calcium IV rescue on day 8. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 and continuing until blood counts recover. Treatment repeats approximately every 14 days for 2 courses.
  • CNS therapy: Patients receive cytarabine intrathecally (IT) with or without hydrocortisone IT on days 1, 4, and 11 of each induction therapy course. Patients with evidence of CNS involvement by lymphoma continue to receive cytarabine IT twice weekly during any induction therapy treatment delay. Patients who demonstrate CSF clearance receive cytarabine IT once weekly for 4 doses and then once every other week for 4 doses during consolidation therapy. Patients with disease progression during induction therapy or persistent CNS involvement by lymphoma are removed from the study. All other patients proceed to consolidation therapy.
  • Consolidation therapy: Patients receive rituximab IV on day -4 and high-dose cyclophosphamide IV on days -3, -2, -1, and 0. Patients receive G-CSF SC once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6. Patients then receive rituximab IV once weekly for 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 3 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Intensified CVP, Rituximab, and High Dose Cyclophosphamide for Adult Burkitt or Burkitt-Like Lymphoma
Actual Study Start Date : July 2005
Actual Primary Completion Date : August 2011
Actual Study Completion Date : August 2013


Arm Intervention/treatment
Experimental: R-CVP + HiCy
Protocol intervention consists of two fifteen-day cycles of cyclophosphamide (Cy), vincristine (V), prednisone (P), rituximab (R), with filgrastim support. CNS intervention consists of three days of cytarabine and hydrocortisone and one day of methotrexate (with leucovorin support) for each cycle. After those two cycles, rituximab and high-dose cyclophosphamide (HiCy) will be given.
Biological: Filgrastim
5 mcg/kg/day starting on Day 3 after each R-CVP cycle and on Day 6 after HiCy.
Other Names:
  • Neupogen
  • G-CSF

Biological: Rituximab
375 mg/m^2 on Day 1 and Day 8 of each R-CVP cycle. 375 mg/m^2 on Day -4 of HiCy and weekly for four weeks after HiCy.
Other Name: Rituxan

Drug: Cyclophosphamide
1500 mg/m^2 on Day 1 of each R-CVP cycle. 50 mg/kg/day on Days -3, -2, -1, and 0 of HiCy.
Other Names:
  • Cytoxan
  • Cy
  • CTX
  • HiCy

Drug: Cytarabine
100 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.
Other Name: Ara-C

Drug: Methotrexate
3 g/m^2 on Day 8 of each cycle of R-CVP.
Other Name: MTX

Drug: Prednisone
100 mg on Days 1-5 of each cycle of R-CVP.
Other Name: Deltasone

Drug: Hydrocortisone
50 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.

Drug: Vincristine
1.4 mg/m^2 on Day 1 of each cycle of R-CVP.
Other Name: Oncovin

Drug: Leucovorin
25 mg four times daily after methotrexate administration. Dosing continues until adequate methotrexate levels are reached.
Other Name: Folinic acid




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Up to 3 months ]
    Number of participants who have a complete or partial remission (2007 International Working Group criteria).

  2. Overall Survival [ Time Frame: 1 year and 3 years ]
    Percentage of participants alive at 1 year and at 3 years.

  3. Event-free Survival [ Time Frame: 1 year and 3 years ]
    Percentage of participants alive without relapse at 1 year and 3 years.

  4. Percentage of Participants Experiencing Grade 3-5 Toxicity [ Time Frame: Up to 2 years ]
    Percentage of participants experiencing at least one grade 3-5 adverse event (by CTCAE 3.0 criteria).


Secondary Outcome Measures :
  1. Relapse Pattern [ Time Frame: Up to 6 months ]
    Percentage of participants experiencing central nervous system (CNS) and systemic relapse.



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:

    • Classic, sporadic Burkitt's lymphoma
    • Burkitt's leukemia (FAB L3 acute lymphoblastic leukemia)
    • Atypical Burkitt/Burkitt's-like lymphoma or leukemia, defined by the following criteria:

      • Characteristic morphologic features
      • High proliferative index AND Ki-67 ≥ 85%
  • Any stage allowed
  • Newly diagnosed or untreated disease

    • Steroids allowed

PATIENT CHARACTERISTICS:

Age

  • 30 and over

Performance status

  • Not specified

Life expectancy

  • Not specified

Renal

  • No known irreversible renal dysfunction that would preclude treatment with high-dose cyclophosphamide

Cardiovascular

  • No known significant cardiac dysfunction that would preclude treatment with high-dose cyclophosphamide

Other

  • Not pregnant or nursing
  • No known HIV positivity
  • No other malignancy within the past 3 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy for lymphoma

    • A maximum of 2 prior doses of intrathecal chemotherapy are allowed

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiation therapy for lymphoma

Surgery

  • Prior complete or incomplete surgical resection of lymphoma allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00133991


Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Pennsylvania
Drexel University College of Medicine - Center City Hahnemann Campus
Philadelphia, Pennsylvania, United States, 19102
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Investigators
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Study Chair: Yvette L. Kasamon, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications of Results:
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00133991     History of Changes
Other Study ID Numbers: J0409
P50CA096888 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
NA_00035765 ( Other Identifier: JHMIRB )
First Posted: August 24, 2005    Key Record Dates
Results First Posted: September 17, 2018
Last Update Posted: September 17, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
untreated adult acute lymphoblastic leukemia
L3 adult acute lymphoblastic leukemia
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage I adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
Additional relevant MeSH terms:
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Burkitt Lymphoma
Lymphoma
Leukemia
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
Cytarabine
Prednisone
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Cyclophosphamide
Rituximab
Methotrexate
Vincristine
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs