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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT00392834
First received: October 25, 2006
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: pegfilgrastim
Biological: rituximab
Drug: cyclophosphamide
Drug: cytarabine
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: leucovorin calcium
Drug: liposomal cytarabine
Drug: methotrexate
Drug: therapeutic hydrocortisone
Drug: vincristine sulfate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Phase II Study of a High Dose, Short Course Regimen (R-CODOX-M/IVAC) Including CNS Penetration and Intensive IT Prophylaxis in HIV-Associated Burkitt's and Atypical Burkitt's Lymphoma

Resource links provided by NLM:


Further study details as provided by AIDS Malignancy Clinical Trials Consortium:

Primary Outcome Measures:
  • Overall Survival (OS) at 1 Year [ Time Frame: 1 year post treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete Response Rate [ Time Frame: 6-8 weeks post treatment, every 4 months post-treatment for 2 years ] [ Designated as safety issue: No ]
  • Failure-free Survival (FFS) [ Time Frame: 6-8 weeks post treatment, every 4 months post-treatment for 2 years ] [ Designated as safety issue: No ]
  • Event-free Survival (EFS) [ Time Frame: 6-8 weeks post treatment, every 4 months post-treatment for 2 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: baseline through 2 years post-treatment ] [ Designated as safety issue: Yes ]
  • Incidence of Infection-related Deaths [ Time Frame: baseline through 2 years post-treatment ] [ Designated as safety issue: No ]
  • Correlation of C-flip Expression, p53 Mutations, and Multidrug Resistance Expression With OS, FFS, and EFS [ Time Frame: baseline through 2 years post-treatment ] [ Designated as safety issue: No ]
  • Utility of Flow Cytometry in Detecting Leptomeningeal Disease [ Time Frame: baseline and 6-8 weeks post-treatment ] [ Designated as safety issue: No ]
  • Degree of Disconcordance Between Flow Cytometry and CNS Cytology Results [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Biologic and Prognostic Significance of Epstein-Barr Virus (EBV) at Diagnosis and Correlation With OS, FFS, and EFS [ Time Frame: baseline through 2 years post-treatment ] [ Designated as safety issue: No ]
  • Correlation of EBV Load Measurements With OS, FFS, and EFS [ Time Frame: baseline through 2 years post-treatment ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: September 2006
Study Completion Date: July 2013
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen A (R-CODOX-M chemotherapy)
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
given subcutaneously
Biological: pegfilgrastim
given subcutaneously
Biological: rituximab
given IV
Drug: cyclophosphamide
given IV
Drug: cytarabine
given intrathecally
Drug: doxorubicin hydrochloride
given IV
Drug: leucovorin calcium
given IV
Drug: liposomal cytarabine
given intrathecally
Drug: methotrexate
given intrathecally
Drug: therapeutic hydrocortisone
given intrathecally
Drug: vincristine sulfate
given IV
Experimental: Regimen B (rituximab and IVAC chemotherapy)
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
given subcutaneously
Biological: pegfilgrastim
given subcutaneously
Biological: rituximab
given IV
Drug: cytarabine
given intrathecally
Drug: etoposide
given IV
Drug: ifosfamide
given IV
Drug: liposomal cytarabine
given intrathecally
Drug: methotrexate
given intrathecally
Drug: therapeutic hydrocortisone
given intrathecally

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00392834

Locations
United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
UCLA Clinical AIDS Research and Education (CARE) Center
Los Angeles, California, United States, 90095-1793
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
UCSF Medical Center at Parnassus
San Francisco, California, United States, 94143-0296
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210-1240
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates, Incorporated - Philadelphia
Philadelphia, Pennsylvania, United States, 19106
United States, Washington
Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center
Seattle, Washington, United States, 98101
United States, West Virginia
West Virginia University Health Sciences Center - Charleston
Charleston, West Virginia, United States, 25304
Sponsors and Collaborators
AIDS Malignancy Clinical Trials Consortium
Investigators
Study Chair: Ariela Noy, MD Memorial Sloan-Kettering Cancer Center
Study Chair: David M. Aboulafia, MD Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center
Study Chair: Lawrence D. Kaplan, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier: NCT00392834     History of Changes
Other Study ID Numbers: CDR0000510918, U01CA070019, AMC-048
Study First Received: October 25, 2006
Results First Received: January 24, 2013
Last Updated: February 6, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by AIDS Malignancy Clinical Trials Consortium:
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

Additional relevant MeSH terms:
Burkitt Lymphoma
Lymphoma
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoma, B-Cell
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cytarabine
Methotrexate
Rituximab
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Doxorubicin
Etoposide
Vincristine
Lenograstim
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate

ClinicalTrials.gov processed this record on April 15, 2014