Rituximab and Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) for Burkitt's and Burkitt's -Like Leukemia/Lymphoma

April 18, 2018 updated by: M.D. Anderson Cancer Center
The goal of this clinical research study is to learn if intensive chemotherapy given over 6 months can help to control or cure Burkitt's leukemia, Burkitt's lymphoma, or small non-cleaved cell B-cell leukemia or lymphoma. Another goal is to see how well this treatment works when given with Rituximab. The safety of the combined treatment will also be studied.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The hyper-CVAD regimen is a combination of chemotherapy drugs including cyclophosphamide, vincristine, Adriamycin, and dexamethasone given together to for one "course" of treatment. This alternates with a course or combination of the chemotherapy drugs methotrexate and cytarabine. Rituximab is a protein (monoclonal antibody) that attaches to the surface of the leukemia or lymphoma cells which have a marker called cluster of differentiation antigen 20 (CD20).

During treatment, participants will have a physical exam and give blood samples (about 1 tablespoon each) at least twice a week. After two courses of chemotherapy, the tests done before treatment will be repeated to check for response. In patients with leukemia, a bone marrow sample will be repeated 2 and 3 weeks from the beginning of treatment to check the response.

All participants in this study will receive 2 kinds of chemotherapy courses for a total of 8 courses. Chemotherapy courses will be given through a large vein by a central venous catheter (a plastic tube usually placed under the collarbone).

In Course 1 (odd course), participants will receive rituximab by vein over 6 hours on Days 1 and 11. Participants will receive the drugs acetaminophen (Tylenol) and diphenhydramine hydrochloride (Benadryl) 30-60 minutes before each dose of rituximab. This will be done to lessen the risk of fever, chills, and allergic reactions. Usually, the first dose of rituximab requires about 6 hours to complete.

Participants will then receive cyclophosphamide by vein over 2-3 hours every 12 hours for a total of 6 doses, given over 3 days (Days 1, 2, and 3). Adriamycin will be given by vein over 24 hours on Day 4. Vincristine will be given by vein over 15 to 30 minutes on Days 4 and 11 along with dexamethasone by mouth or by vein on Days 1-4 and 11-14.

Participants will also receive pegfilgrastim or G-CSF (growth stimulating colony factor) to help with rapid recovery of the normal bone marrow starting after each course of chemotherapy is finished. Pegfilgrastim is injected under the skin within 72 hours of completion of each cycle of chemotherapy. G-CSF is given by injections by vein or under the skin until the blood counts recover.

Treatment to the brain will be given inside the spinal fluid with cytarabine and methotrexate about Days 2 and 7 of the course to help prevent the leukemia from developing there.

For patients 60 years or older, the first course will be given in a protective isolation room to decrease the risk of infection(s).

In Course 2 (even course), participants will receive rituximab by infusion over about 4 hours on Days 1 and 8. They will receive methotrexate by infusion over 24 hours on the first day, and cytarabine in a high dose over 2 hours every 12 hours for 4 doses (Days 2 and 3). Citrovorum factor (leucovorin) will be given by vein or by mouth for 2-3 days (Day 2 and on) to decrease the risk of side effects of methotrexate. G-CSF will be given as in Course 1 (after the chemotherapy is finished). The treatment to the brain inside the spinal fluid will be given as in course 1 on days 2 and 7.

After two courses of therapy, the response to the treatment will be checked. If the leukemia or lymphoma is responding, the therapy will be continued for a total of 8 courses over 6 months. Therapy will be stopped if the leukemia or lymphoma starts to get worse.

An Ommaya reservoir may also be placed surgically as a route to treat leukemia in the brain or to decrease the risk of leukemia in patients who have difficulty with the spinal treatments. An Ommaya reservoir is a tube inserted under the skin of the scalp that enters into the spinal fluid cavity of the brain.

This is an investigational study. All drugs in this study are commercially available. Their use together in this study is investigational. About 70 patients or more will take part in this study. All will be enrolled at MD Anderson.

Study Type

Interventional

Enrollment (Actual)

56

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
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas M. D. Anderson 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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Burkitt's or Burkitt-like leukemia and/or lymphoma, either previously untreated, previously treated (may be in CR or with active disease after 1-2 courses of chemotherapy), or HIV-related.
  2. All ages are eligible.
  3. Zubrod performance status < 3 (ECOG Scale, Appendix A).
  4. Adequate liver function (bilirubin < 3.0 mg/dL, unless considered due to tumor), and renal function (creatinine < 3.0 mg/dL, unless considered due to tumor).
  5. Signed informed consent.

Exclusion Criteria:

1) N/A

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: Hyper-CVAD
Hyper-CVAD (odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Rituximab 375 mg/m2 days 1 +/- 2 days and 11 +/- 2 days for the odd courses of therapy, and days 1 +/- 2 days and 8 +/- 2 days for the even courses of therapy, first 4 courses. Cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3. Doxorubicin 50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses). Vincristine 2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses). Dexamethasone 40 mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses). G-CSF 10 mg/kg/day (rounded) until neutrophil recovery 1 x 10^9/L or higher can be substituted or can be added to pegfilgrastim if neutrophils have not recovered to 1 x 10^9/L by day 21.
Drug: Rituximab
375 mg/m2 IV days 1 +/- 2 days and 11 +/- 2 days for the odd courses of therapy, and days 1 +/- 2 days and 8 +/- 2 days for the even courses of therapy, first 4 courses.
Other Names:
  • Rituxan
Drug: Cyclophosphamide
300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3 (total dose 1800 mg/m2) starting after rituximab completed (odd courses).
Other Names:
  • Cytoxan
  • Neosar
Drug: Doxorubicin
50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses).
Other Names:
  • Adriamycin
  • Rubex
Drug: Vincristine
2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses)
Other Names:
  • Oncovin
  • Vincasar Pfs
Drug: Dexamethasone
40mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses)
Other Names:
  • Decadron
Drug: G-CSF
10 mcg/kg
Other Names:
  • Filgrastim
  • Neupogen
Drug: Cytarabine
100 mg intrathecal day 7 +/- 2 days (odd courses); 3 gm/m2 IV over 2 hours every 12 hours for 4 doses on days 2, 3 (even courses).
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride
Drug: Methotrexate
200 mg/m2 IV over 2 hrs followed by 800 mg/m2 over 22 hrs on day 1 after the completion of Rituximab.
Other Names:
  • Rheumatrex
  • Methotrexate Sodium, MTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Remission Rate: Percentage of Participants With Complete Remission (CR)
Time Frame: After two 21-day courses, response to treatment checked for Complete Remission (CR)
Complete Remission (CR) was defined as the presence of 5% or less blasts in the bone marrow, with a granulocyte count ≥1.0 × 10^9/L, a platelet count ≥100 × 10^9/L, and no extramedullary disease. Complete recovery except platelets (CRp) was defined as for CR, except for recovery of platelet count to <100 × 10^9/L. Partial remission (PR) was defined as a bone marrow with >5% and <25% blasts with a granulocyte count of ≥1.0 × 109/L and a platelet count of ≥100 × 10^9/L. Relapse was defined by recurrence of more than 5% lymphoblasts in the bone marrow aspirate or by the presence of extramedullary disease after achieving CR.
After two 21-day courses, response to treatment checked for Complete Remission (CR)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate: Percentage of Participants With Complete Remission (CR) or Partial Remission (PR)
Time Frame: After two 21-day courses, response to treatment checked for Complete Remission (CR)
Complete Remission (CR) was defined as the presence of 5% or less blasts in the bone marrow, with a granulocyte count ≥1.0 × 10^9/L, a platelet count ≥100 × 10^9/L, and no extramedullary disease. Complete recovery except platelets (CRp) was defined as for CR, except for recovery of platelet count to <100 × 10^9/L. Partial remission (PR) was defined as a bone marrow with >5% and <25% blasts with a granulocyte count of ≥1.0 × 109/L and a platelet count of ≥100 × 10^9/L. Relapse was defined by recurrence of more than 5% lymphoblasts in the bone marrow aspirate or by the presence of extramedullary disease after achieving CR.
After two 21-day courses, response to treatment checked for Complete Remission (CR)

Collaborators and Investigators

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

Sponsor

M.D. Anderson Cancer Center

Investigators

  • Principal Investigator: Susan O'Brien, MD, M.D. Anderson Cancer Center

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.

Helpful Links

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

August 1, 2002

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

April 28, 2008

First Submitted That Met QC Criteria

April 30, 2008

First Posted (Estimate)

May 1, 2008

Study Record Updates

Last Update Posted (Actual)

May 16, 2018

Last Update Submitted That Met QC Criteria

April 18, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ID02-229
  • NCI-2010-01455 (Registry Identifier: NCI CTRP)

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