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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: August 22, 2014
Last verified: August 2014

October 25, 2006
August 22, 2014
October 2006
October 2015   (final data collection date for primary outcome measure)
  • 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
Not Provided
Complete list of historical versions of study NCT00392990 on ClinicalTrials.gov Archive Site
  • 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
Not Provided
Not Provided
Not Provided
 
Doxorubicin Hydrochloride Liposome and Rituximab With Combination Chemotherapy in Treating Patients With Newly Diagnosed Burkitt's Lymphoma or Burkitt-Like Lymphoma
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

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • 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
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.
Interventions:
  • Drug: Regimen A
  • Drug: Regimen B
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
25
October 2016
October 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00392990
NU 06H2, P30CA060553, NU 06H2, NU-1346-018, ORTHO-NU-06H2, CDR0000509706, STU00004480
Yes
Northwestern University
Northwestern University
National Cancer Institute (NCI)
Principal Investigator: Leo Gordon, MD Northwestern University
Northwestern University
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP