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LymphomaPhase 2NCT00392990

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

A Phase 2 study testing Regimen A and Regimen B in people with Lymphoma, run by Northwestern University at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma
What is being tested?
Regimen A and Regimen B
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
8 sitesUnited States
Study dates
6 Feb 2007to 28 May 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Robert H. Lurie Comprehensive Cancer Center at Northwestern University

    Chicago, Illinois, 60611-3013

  • John H. Stroger Cook County Hospital

    Chicago, Illinois, 60612

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University Hospitals Case Medical Center

    Cleveland, Ohio, 44106

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • The Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

  • Advocate Lutheran General Cancer Care Center

    Park Ridge, Illinois, 60068-1174

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Lymphoma
Being tested
Regimen A, Regimen B
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
Medical subject headings
Lymphoma, Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Regimen ADrug

    Also called Rituximab, Doxil, pegylated liposomal doxorubicin, cyclophosphamide

    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

  • Regimen BDrug

    Also called Rituximab, Ifosfamide, Ifex®, Etoposide

    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)

Study groups in NCT00392990
Study groupRoleWhat they receive
Alternating doxil/Magrath regimen & rituximab/Magrath regimenExperimentalPatients 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.
Receives: Drug: Regimen A; Drug: Regimen B

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR) of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen

    Response Rate is defined as combined number of patients with Complete Remission (CR) Complete Remission undetermined (Cru) and Partial Remission (PR) for patients with Burkitt's and Burkitt-like Lymphoma/Leukemia. Response will be measured by CT scans following treatment completion and assessed using Response Criteria for Non-Hodgkin's Lymphoma where:

    CR=complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms.

    CRu=same as above but allowing for 75% decrease in lymph node masses and indeterminate or normal bone marrow.

    PR=50% decrease in SPD of the six largest dominant nodes or nodal masses with no increase in size or other nodes, liver, spleen and no new sites of disease.

    Measured: After two cycles of treatment and at completion of treatment (4 cycles for high risk and 3 cycles for low risk) up to approximately 20 weeks.

Secondary outcomes (3)

  1. Overall Survival (OS) of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen

    Overall Survival (OS) of patients with Burkitt's and Burkitt-like Lymphoma/Leukemia treated with modified Magrath regimen. OS is defined from the first dose of study drug to the time of death for any reason.

    Measured: At 2 years from treatment initiation Median follow up 34 months (range 15-45)

  2. Safety of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen (Addition of Rituximab, Subsitution of Adriamycin for Doxil and Using Lower Dose of Methotrexate)

    Adverse events (AE) graded as either 3 or 4 and determined to be at least possibly related to study treatment will be collected in patients Burkitt's and Burkitt-like Lymphoma/Leukemia treated with modified Magrath regimen to assess the safety and toxicity profile of the addition of rituximab, subsitution of adriamycin for doxil and lower dose of methotrexate. AEs will be assessed as follows at the following time points: At the end of each cycle or monthly whichever is less frequent and 30 days post last dose of study treatment for a maximum of 3 cycles for regimen A and 4 cycles for regimen B and up to 12 months.

    In general AEs will be assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v 3.0). In general adverse events (AEs) will be graded according to the following:

    Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

    Measured: After each cycle or monthly (whichever is less frequent), 30 days post last dose. Treatment duration was at a median of 13 weeks (range 11-20) for high-risk patients and 10 weeks (range 9-12) for low-risk patients.

  3. Progression Free Survival (PFS) of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen

    Progression Free Survival (PFS) will be defined from the first dose of study drug to the first documentation of progressive disease or death for any reason. Patients that are lost to follow-up before progression will be censored at the point of last documentation of not experiencing the event.

    Measured: At 2 years from treatment initiation. Median follow up 34 months (range 15-45)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2006 (estimated)
  2. Study start6 Feb 2007
  3. Primary completion3 Dec 2011
  4. Study completion28 May 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00392990
Sponsor's protocol ID
NU 06H2
Other IDs
P30CA060553, NU 06H2, NU-1346-018, ORTHO-NU-06H2, CDR0000509706, STU00004480
Status last verified
Aug 2019
First submitted
25 Oct 2006
Last updated
15 Oct 2019
Data monitoring committee
Yes

Publications

  • Evens AM, Carson KR, Kolesar J, Nabhan C, Helenowski I, Islam N, Jovanovic B, Barr PM, Caimi PF, Gregory SA, Gordon LI. A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma. Ann Oncol. 2013 Dec;24(12):3076-81. doi: 10.1093/annonc/mdt414. Epub 2013 Oct 20.

    PubMed 24146219

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regimen A and Regimen B in people with Lymphoma, run by Northwestern University at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen (time frame: After two cycles of treatment and at completion of treatment (4 cycles for high risk and 3 cycles for low risk) up to approximately 20 weeks.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00392990, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2019.

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