Doxorubicin Hydrochloride Liposome and Rituximab With Combination Chemotherapy in Treating Patients With Newly Diagnosed Burkitt's Lymphoma or Burkitt-Like Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Northwestern University
ClinicalTrials.gov Identifier:
NCT00392990
First received: October 25, 2006
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving doxorubicin hydrochloride liposome and rituximab together with combination chemotherapy works in treating patients with newly diagnosed Burkitt's lymphoma or Burkitt-like lymphoma.


Condition Intervention Phase
Lymphoma
Drug: Regimen A
Drug: Regimen B
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: A Multicenter Phase II Study Incorporating DOXIL® and Rituximab Into the Magrath Regimen for HIV-Negative and HIV-Positive Patients With Newly Diagnosed Burkitt's and Burkitt-like Lymphoma

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Response rate: complete remission rate [ Time Frame: every 6 months up to two years after treatment completion ] [ Designated as safety issue: No ]
    Response rate will be accessed by CT scans every six months up to two years following completion of treatment

  • Overall response rate: disease free and overall survival [ Time Frame: every six months up to two years following treatment completion ] [ Designated as safety issue: No ]
    Overall response rate (including disease free and overall survival)will be assessed by CT scans every six months up to two years following treatment completion


Secondary Outcome Measures:
  • Safety of Rituximab plus Magrath regimen in HIV negative and HIV positive subjects [ Time Frame: Regimen A prior to cycles 1 and 3; Regimen B prior to cycles 2 and 4; 30 days after completion of treatment ] [ Designated as safety issue: Yes ]
    adverse events will be assessed as follows: Regimen A prior to cycles 1 and 3; Regimen B prior to cycles 2 and 4; 30 days after completion of treatment

  • Safety of using doxil in place of adriamycin [ Time Frame: Regimen A prior to cycles 1 and 3 and 30 days after completion of treatment ] [ Designated as safety issue: Yes ]
    Adverse events will be assessed as follows: Regimen A prior to cycles 1 and 3 and 30 days after completion of treatment

  • Safety of using lower intravenous methotrexate dosing [ Time Frame: Regimen A prior to cycles 1 and 3 and 30 days after completion of treatment ] [ Designated as safety issue: Yes ]
    Adverse events will be assessed as follows: Regimen A prior to cycles 1 and 3 and 30 days after completion of treatment


Estimated Enrollment: 25
Study Start Date: October 2006
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alternating doxil/Magrath regimen & rituximab/Magrath regimen
Patients are stratified between high risk and low risk disease status. Low risk patients receive 3 cycles of rituximab (500 mg/m2) R-CODOX-M chemotherapy IV over 2-4 hours with intrathecal chemotherapy (Regimen A). High risk patients receive 1 cycle of R-CODOX-M chemotherapy IV followed by R-IVAC chemotherapy over 30 minutes(Regimen B); regimens A and B are then repeated.
Drug: Regimen A
Cyclophosphamide (800 mg/m2 IV over 1 hour)+ vincristine (1.5 mg/m2 IV PUSH)+ doxorubicin (40 mg/m2 IV)+ high-dose methotrexate (2,700 mg/m2 IV over 23 hours)+ rituximab (500 mg/m2 IV)(R-CODOX-M) regimen
Other Names:
  • Rituximab
  • Doxil
  • pegylated liposomal doxorubicin
  • cyclophosphamide
  • Cytoxan®
  • CTX
  • CPM
  • Neosar®
  • Vincristine
  • Oncovin®
  • Vincasar PFS®
  • vincristine sulphate
  • VCR
  • leucocristine
  • LCR
  • Methotrexate
  • Methotrexate sodium
  • MTX
  • Mexate
  • Mexate-AQ
  • Folex
  • Folex PFS
  • Abitrexate
  • Rheumatrex
  • Amethopterin
Drug: Regimen B
Rituximab (500 mg/m2 IV once)+ Ifosfamide (1500 mg/m2 IV daily over 3 hours)+ Etoposide (60 mg/m2 IV daily over 1 hour), and Cytarabine (2 grams/m2 IV over 3 hours for 4 doses)
Other Names:
  • Rituximab
  • Ifosfamide
  • Ifex®
  • Etoposide
  • VP-16
  • VePesid®
  • VP-16-213
  • EPEG
  • epipodophyllotoxin
  • NSC # 141540
  • Cytarabine
  • Cytosar-U
  • Ara-C
  • Arabinosyl
  • cytosine arabinoside

Detailed Description:

OBJECTIVES:

Primary

  • Determine the overall response rate (complete remission, complete remission undetermined, and partial remission) in HIV-negative or HIV-positive patients with newly diagnosed Burkitt's or Burkitt-like lymphoma treated with doxorubicin hydrochloride liposome and rituximab as part of the Magrath regimen.

Secondary

  • Determine the complete remission rate in patients treated with this regimen.
  • Determine progression-free and overall survival at 2 years in patients treated with this regimen.
  • Determine the safety of adding rituximab to the standard Magrath regimen in these patients.
  • Determine the safety of using doxorubicin hydrochloride liposome in place of doxorubicin hydrochloride in these patients.
  • Determine correlative levels of rituximab and doxorubicin hydrochloride liposome in cerebrospinal fluid and peripheral blood.

OUTLINE: This is a multicenter study. Patients are stratified according to risk category (low risk vs high risk). Patients are assigned to 1 of 2 treatment regimens according to stratum.

  • Regimen A (low-risk disease with no CNS involvement): Patients receive R-CODOX-M chemotherapy comprising rituximab IV over 2-4 hours on days 0 and 8; doxorubicin hydrochloride liposome IV over 30 minutes on day 1; vincristine IV on days 1 and 8; cyclophosphamide IV over 1 hour on days 1-5; and high-dose methotrexate (MTX) IV over 24 hours on day 10. Patients also receive leucovorin calcium IV beginning 36 hours after the start of MTX infusion and continuing every 6 hours until blood levels of MTX are safe. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily on days 4-8 in courses 1 and 3 and on days 6 and 7 in course 2. Beginning on day 12, daily G-CSF dosing resumes until blood counts recover. Patients receive CNS prophylaxis comprising cytarabine intrathecally (IT) on day 1 and MTX IT on day 3. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
  • Regimen B (high-risk disease with or without CNS involvement): Patients receive R-CODOX-M chemotherapy with leucovorin calcium and G-CSF support as in regimen A for courses 1 and 3 and R-IVAC chemotherapy with leucovorin calcium and G-CSF support (as below) for courses 2 and 4. R-IVAC chemotherapy comprises high-dose ifosfamide IV over 3 hours and etoposide IV over 1 hour on days 1-5; cytarabine IV over 3 hours twice daily on days 2 and 3; and rituximab IV over 2-4 hours on day 0 and on day 6 or 7. Patients also receive leucovorin calcium orally every 6 hours on day 6 and G-CSF SC once daily beginning on day 6 or 7 and continuing until blood counts recover. Patients without CNS involvement receive CNS prophylaxis comprising cytarabine IT on days 1 and 3 and MTX IT on day 15 in courses 1 and 3 and MTX IT alone on day 5 in courses 2 and 4. Patients with proven CNS involvement at diagnosis receive cytarabine IT on days 1, 3, and 5 in course 1, on days 7 and 9 in course 2, and on days 1 and 3 in course 3. These patients also receive MTX IT on days 15 and 17 in course 1, on day 5 in courses 2 and 4, and on day 15 in course 3. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

The first 10 patients enrolled on the study undergo cerebrospinal fluid and blood collection during courses 1 and 3 for correlative biological marker and pharmacological studies.

After completion of study treatment, patients are followed at 30 days and then periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

  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 or Burkitt-like non-Hodgkin's lymphoma meeting 1 of the following risk criteria:

    • Low-risk disease meeting all of the following criteria:

      • Normal lactate dehydrogenase level
      • ECOG performance status 0-1
      • Ann Arbor stage I or II
      • No tumor mass over 10 cm in greatest diameter
    • High-risk disease, defined as disease not meeting low-risk criteria
  • Newly diagnosed disease

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Hemoglobin ≥ 8.0 g/dL
  • Absolute neutrophil count ≥ 500/mm³
  • Platelet count ≥ 100,000/mm³ (50,000/mm³ if bone marrow involvement is documented)
  • AST and ALT ≤ 3 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 3 times ULN
  • Bilirubin ≤ 1.5 times ULN (3 times ULN if liver metastases are present)
  • Creatinine clearance > 50 mL/min
  • Creatinine ≤ 2.0 mg/dL
  • LVEF ≥ 45% by MUGA scan or echocardiogram
  • No New York Heart Association class II-IV heart failure
  • No clinically significant pericardial disease
  • No myocardial infarction within the past 6 months
  • No uncontrolled angina
  • No severe uncontrolled ventricular arrhythmias
  • No ECG evidence of acute ischemia or active conduction system abnormalities

    • Investigator must document any baseline ECG abnormality as not medically relevant
  • No other malignancy within the past year except for basal cell carcinoma of the skin or in situ carcinoma of the cervix
  • No other serious medical or psychiatric illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

  • Prior treatment with 1 course of any combination of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and/or prednisone* (CHOP)-like therapy allowed, provided the following doses are not exceeded:

    • Rituximab 750 mg/m²
    • Cyclophosphamide 1,000 mg/m²
    • Doxorubicin hydrochloride 50 mg/m²
    • Vincristine 2 mg/m²
  • No other investigational drugs within the past 14 days
  • No other concurrent systemic, cytotoxic, investigational, or chemotherapy agents NOTE: *No maximum dose restriction on steroids
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00392990

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Rush University Medical Center
Chicago, Illinois, United States, 60612
John H. Stroger Cook County Hospital
Chicago, Illinois, United States, 60612
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Advocate Lutheran General Cancer Care Center
Park Ridge, Illinois, United States, 60068-1174
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, New Jersey
The Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Leo Gordon, MD Northwestern University
  More Information

No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00392990     History of Changes
Other Study ID Numbers: NU 06H2, P30CA060553, NU 06H2, NU-1346-018, ORTHO-NU-06H2, CDR0000509706, STU00004480
Study First Received: October 25, 2006
Last Updated: July 18, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Northwestern University:
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
Doxorubicin
Etoposide
Podophyllotoxin
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 21, 2014