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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Lymphoma

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate: complete remission rate

Outcome Description:

Response rate will be accessed by CT scans every six months up to two years following completion of treatment

Outcome Time Frame:

every 6 months up to two years after treatment completion

Safety Issue:

No

Principal Investigator

Leo Gordon, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Northwestern University

Authority:

United States: Food and Drug Administration

Study ID:

NU 06H2

NCT ID:

NCT00392990

Start Date:

October 2006

Completion Date:

October 2016

Related Keywords:

  • Lymphoma
  • 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
  • Burkitt Lymphoma
  • Lymphoma

Name

Location

Loyola University Medical CenterMaywood, Illinois  60153
Rush University Medical CenterChicago, Illinois  60612-3824
Advocate Lutheran General Cancer Care CenterPark Ridge, Illinois  60068-1174
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Washington UniversitySt. Louis, Missouri  63110
The Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
University Hospitals Case Medical CenterCleveland, Ohio  44106
John H. Stroger Cook County HospitalChicago, Illinois  60612