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

September 13, 2018 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase II Study of Intensified CVP, Rituximab, and High Dose Cyclophosphamide for Adult Burkitt or Burkitt-Like Lymphoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

23

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
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19102
        • Drexel University College of Medicine - Center City Hahnemann Campus

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

30 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: 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:
  • G-CSF
  • Neupogen
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 Names:
  • 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
  • CTX
  • Cy
  • HiCy
Drug: Cytarabine
100 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.
Other Names:
  • Ara-C
Drug: Methotrexate
3 g/m^2 on Day 8 of each cycle of R-CVP.
Other Names:
  • MTX
Drug: Prednisone
100 mg on Days 1-5 of each cycle of R-CVP.
Other Names:
  • 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 Names:
  • Oncovin
Drug: Leucovorin
25 mg four times daily after methotrexate administration. Dosing continues until adequate methotrexate levels are reached.
Other Names:
  • Folinic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: Up to 3 months
Number of participants who have a complete or partial remission (2007 International Working Group criteria).
Up to 3 months
Overall Survival
Time Frame: 1 year and 3 years
Percentage of participants alive at 1 year and at 3 years.
1 year and 3 years
Event-free Survival
Time Frame: 1 year and 3 years
Percentage of participants alive without relapse at 1 year and 3 years.
1 year and 3 years
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).
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse Pattern
Time Frame: Up to 6 months
Percentage of participants experiencing central nervous system (CNS) and systemic relapse.
Up to 6 months

Collaborators and Investigators

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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Yvette L. Kasamon, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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 (Actual)

July 1, 2005

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

August 22, 2005

First Submitted That Met QC Criteria

August 22, 2005

First Posted (Estimate)

August 24, 2005

Study Record Updates

Last Update Posted (Actual)

September 17, 2018

Last Update Submitted That Met QC Criteria

September 13, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J0409
  • P30CA006973 (U.S. NIH Grant/Contract)
  • P50CA096888 (U.S. NIH Grant/Contract)
  • NA_00035765 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

Subscribe