Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed, HIV-Associated Burkitt's Lymphoma

NCT00392834 | Completed Phase 2 Results

• 3 other identifiers: AMC-048U01CA070019CDR0000510918
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 13

Brief Summary

RATIONALE: 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. 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 rituximab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with newly diagnosed, HIV-associated Burkitt's lymphoma.

Conditions

Lymphoma

Keywords

stage I adult Burkitt lymphoma; stage III adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; contiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult Burkitt lymphoma; AIDS-related peripheral/systemic lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) at 1 Year

  1 year post treatment

Secondary Outcomes (10)

• Complete Response Rate

  6-8 weeks post treatment, every 4 months post-treatment for 2 years

• Failure-free Survival (FFS)

  6-8 weeks post treatment, every 4 months post-treatment for 2 years

• Event-free Survival (EFS)

  6-8 weeks post treatment, every 4 months post-treatment for 2 years

• Toxicity

  baseline through 2 years post-treatment

• Incidence of Infection-related Deaths

  baseline through 2 years post-treatment

Study Arms (2)

Regimen A (R-CODOX-M chemotherapy)

EXPERIMENTAL

Patients receive rituximab IV and doxorubicin hydrochloride IV over 15 minutes on day 1, cyclophosphamide IV over 30-60 minutes on days 1 and 2, pegfilgrastim SC on day 3, vincristine IV on days 1 and 8, high-dose methotrexate IV over 2-4 hours on day 15, and leucovorin calcium IV beginning 24 hours after the start of methotrexate and continuing every 6 hours until level is adequate. Patients receive CNS prophylaxis of methotrexate IT, cytarabine IT, and hydrocortisone IT on day 1. Patients with high-risk disease receive an additional dose of cytarabine IT on day 3. Patients also receive G-CSF SC once daily on days 3-9. Once the methotrexate levels drops below 50 nmol/L, patients resume G-CSF SC once daily beginning on approximately day 18 and continuing until blood counts recover.

Biological: filgrastim; Biological: pegfilgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: cytarabine; Drug: doxorubicin hydrochloride; Drug: leucovorin calcium; Drug: liposomal cytarabine; Drug: methotrexate; Drug: therapeutic hydrocortisone; Drug: vincristine sulfate

Regimen B (rituximab and IVAC chemotherapy)

EXPERIMENTAL

Patients receive rituximab IV on day 1, ifosfamide IV continuously and etoposide IV continuously over 24 hours on days 1-5, and high-dose cytarabine IV over 1-3 hours twice daily on days 1-2. Patients receive CNS prophylaxis comprising methotrexate IT and hydrocortisone IT on day 5. Patients also receive pegfilgrastim SC once 24-48 hours after completion of chemotherapy OR G-CSF SC beginning on day 6 and continuing until blood counts recover. Patients with CNS involvement (leptomeningeal and/or intraparenchymal) at diagnosis do not receive CNS prophylaxis as above. Instead, these patients receive a combination of sequential liposomal cytarabine and methotrexate IT or via an Ommaya reservoir on day 1 and then every 14 days as tolerated until completion of systemic chemotherapy.

Biological: filgrastim; Biological: pegfilgrastim; Biological: rituximab; Drug: cytarabine; Drug: etoposide; Drug: ifosfamide; Drug: liposomal cytarabine; Drug: methotrexate; Drug: therapeutic hydrocortisone

Interventions

filgrastim BIOLOGICAL

given subcutaneously

Regimen A (R-CODOX-M chemotherapy); Regimen B (rituximab and IVAC chemotherapy)

pegfilgrastim BIOLOGICAL

given subcutaneously

Regimen A (R-CODOX-M chemotherapy); Regimen B (rituximab and IVAC chemotherapy)

rituximab BIOLOGICAL

given IV

Regimen A (R-CODOX-M chemotherapy); Regimen B (rituximab and IVAC chemotherapy)

cyclophosphamide DRUG

given IV

Regimen A (R-CODOX-M chemotherapy)

cytarabine DRUG

given intrathecally

Regimen A (R-CODOX-M chemotherapy); Regimen B (rituximab and IVAC chemotherapy)

doxorubicin hydrochloride DRUG

given IV

Regimen A (R-CODOX-M chemotherapy)

etoposide DRUG

given IV

Regimen B (rituximab and IVAC chemotherapy)

ifosfamide DRUG

given IV

Regimen B (rituximab and IVAC chemotherapy)

leucovorin calcium DRUG

given IV

Regimen A (R-CODOX-M chemotherapy)

liposomal cytarabine DRUG

given intrathecally

Regimen A (R-CODOX-M chemotherapy); Regimen B (rituximab and IVAC chemotherapy)

methotrexate DRUG

given intrathecally

Regimen A (R-CODOX-M chemotherapy); Regimen B (rituximab and IVAC chemotherapy)

therapeutic hydrocortisone DRUG

given intrathecally

Regimen A (R-CODOX-M chemotherapy); Regimen B (rituximab and IVAC chemotherapy)

vincristine sulfate DRUG

given IV

Regimen A (R-CODOX-M chemotherapy)

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed Burkitt's lymphoma (BL) or new WHO 2009 criteria B-cell lymphoma unclassified (with features intermediated between difuse large B-cell lymphoma and BL) * Any stage disease * Newly diagnosed disease * Meets 1 of the following criteria for disease risk: * Low-risk disease, defined by 1 of the following: * Stage I with a single focus of disease \< 10 cm AND normal lactate dehydrogenase (LDH) level * Totally resected intra-abdominal disease only AND normal LDH post surgery * High-risk disease, defined as not meeting criteria for low-risk disease * Measurable or nonmeasurable disease * HIV-positive confirmed by enzyme-linked immunosorbent assay and Western blot OR by measurable HIV viral load * No visceral Kaposi's sarcoma PATIENT CHARACTERISTICS: * Karnofsky performance status 40-100% * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * LVEF ≥ 50% by MUGA or echocardiogram * Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min * Absolute neutrophil count ≥ 1,000/mm³ * Platelet count ≥ 50,000/mm³ (unless related to lymphoma)\* * Direct bilirubin ≤ 2.0 mg/dL OR total bilirubin ≤ 3.5 mg/dL AND direct bilirubin normal (if elevated bilirubin secondary to antiretroviral therapy) * AST and ALT ≤ 3 times upper limit of normal * No other malignancy within the past 5 years except curatively treated cutaneous basal cell or squamous cell carcinoma, carcinoma in situ of the cervix, or cutaneous Kaposi's sarcoma * No other medical illness unrelated to non-Hodgkin's lymphoma, including any of the following: * Uncontrolled infection (including opportunistic infection) * Chronic renal insufficiency * Myocardial infarction within the past 6 months * Unstable angina * Cardiac arrhythmias other than chronic atrial fibrillation * Patients with active hepatitis B infection are eligible provided they receive concurrent dual antiviral therapy NOTE: \*Patients with bone marrow involvement are eligible irrespective of blood count PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior therapy for this disease except for 1 of the following : * Seven consecutive days of steroids alone or in combination with a non-CHOP regimen necessary for patient stabilization (e.g., cyclophosphamide and steroids steroids for normalization of disease-related hyperbilirubinemia) * One course of CHOP or fractionated CHOP (e.g. CODOX) with or without rituximab * No epoetin alfa or filgrastim (G-CSF) within 24 hours of study chemotherapy * No concurrent zidovudine

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• The Emmes Company, LLC: collaborator

Study Sites (13)

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, 92093-0658, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

UCLA Clinical AIDS Research and Education (CARE) Center

Los Angeles, California, 90095-1793, United States

Location

UCSF Medical Center at Parnassus

San Francisco, California, 94143-0296, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210-1240, United States

Location

Pennsylvania Oncology Hematology Associates, Incorporated - Philadelphia

Philadelphia, Pennsylvania, 19106, United States

Location

Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

West Virginia University Health Sciences Center - Charleston

Charleston, West Virginia, 25304, United States

Location

Related Publications (1)

• Noy A, Lee JY, Cesarman E, Ambinder R, Baiocchi R, Reid E, Ratner L, Wagner-Johnston N, Kaplan L; AIDS Malignancy Consortium. AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma. Blood. 2015 Jul 9;126(2):160-6. doi: 10.1182/blood-2015-01-623900. Epub 2015 May 8.

  PMID: 25957391 RESULT

MeSH Terms

Conditions

Lymphoma; Burkitt Lymphoma

Interventions

Filgrastim; pegfilgrastim; Rituximab; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Ifosfamide; Leucovorin; Methotrexate; Hydrocortisone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and 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

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Oxazines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Aminopterin; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Jeannette Lee, Ph.D.
• Organization: University of Arkansas for Medical Sciences

jylee@uams.edu

501-526-6712

Study Officials

• Ariela Noy, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

• David M. Aboulafia, MD

  Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center

  STUDY CHAIR

• Lawrence D. Kaplan, MD

  University of California, San Francisco

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: September 1, 2006
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2013
• Last Updated: June 6, 2018
• Results First Posted: February 28, 2013

Record last verified: 2018-05

Locations

US (13)