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

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ClinicalTrials.gov Identifier: NCT00669877

Recruitment Status : Completed

First Posted : May 1, 2008

Results First Posted : May 16, 2018

Last Update Posted : May 16, 2018

Sponsor:

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Burkitt's Lymphoma Burkitt'S-like Lymphoma	Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Dexamethasone Drug: G-CSF Drug: Cytarabine Drug: Methotrexate	Phase 2

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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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	56 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Rituximab and Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) for Burkitt's and Burkitt's -Like Leukemia/Lymphoma
Study Start Date :	August 2002
Actual Primary Completion Date :	October 2015
Actual Study Completion Date :	October 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia Lymphoma

Drug Information available for: Dexamethasone Cyclophosphamide Vincristine sulfate Rituximab

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Burkitt Lymphoma B-cell Lymphoma

U.S. FDA Resources

Arms and Interventions

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 Name: 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 Name: 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

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 Name: 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 Name: 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

Outcome Measures

Primary Outcome Measures :

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.

Other Outcome Measures:

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.

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.
All ages are eligible.
Zubrod performance status < 3 (ECOG Scale, Appendix A).
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).
Signed informed consent.

Exclusion Criteria:

1) N/A

Contacts and Locations

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): NCT00669877

Locations

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

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

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

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

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Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00669877
Other Study ID Numbers:	ID02-229 NCI-2010-01455 ( Registry Identifier: NCI CTRP )
First Posted:	May 1, 2008 Key Record Dates
Results First Posted:	May 16, 2018
Last Update Posted:	May 16, 2018
Last Verified:	April 2018

Keywords provided by M.D. Anderson Cancer Center:


Burkitt's Lymphoma Burkitt's Like Lymphoma Leukemia Hyper-CVAD	Rituximab Methotrexate Cytarabine

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 Infections Tumor Virus Infections	Lymphoma, B-Cell Lymphoma, Non-Hodgkin Cytarabine Dexamethasone Cyclophosphamide Rituximab Doxorubicin Methotrexate Vincristine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents

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