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

NCT ID: NCT00669877

Last Updated: 2018-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-08-31
• Study Completion Date: 2015-10-31

Brief Summary

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.

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.

Conditions

Burkitt's Lymphoma; Burkitt'S-like Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

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.

Cyclophosphamide

Intervention Type: DRUG

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).

Doxorubicin

Intervention Type: DRUG

50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses).

Vincristine

Intervention Type: DRUG

2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses)

Dexamethasone

Intervention Type: DRUG

40mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses)

G-CSF

Intervention Type: DRUG

10 mcg/kg

Cytarabine

Intervention Type: DRUG

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).

Methotrexate

Intervention Type: DRUG

200 mg/m2 IV over 2 hrs followed by 800 mg/m2 over 22 hrs on day 1 after the completion of Rituximab.

Interventions

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.

Intervention Type: 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).

Intervention Type: DRUG

Doxorubicin

50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses).

Intervention Type: DRUG

Vincristine

2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses)

Intervention Type: DRUG

Dexamethasone

40mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses)

Intervention Type: DRUG

G-CSF

10 mcg/kg

Intervention Type: 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).

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Rituxan; Cytoxan; Neosar; Adriamycin; Rubex; Oncovin; Vincasar Pfs; Decadron; Filgrastim; Neupogen; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride; Rheumatrex; Methotrexate Sodium, MTX

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan O'Brien, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

NCI-2010-01455

Identifier Type: REGISTRY

Identifier Source: secondary_id

ID02-229

Identifier Type: -

Identifier Source: org_study_id