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

NCT00392990 | Completed Phase 2 Results DMC

• 6 other identifiers: NU 06H2P30CA060553NU-1346-018ORTHO-NU-06H2CDR0000509706STU00004480
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 8

Brief 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. 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.

Conditions

Lymphoma

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

Outcome Measures

Primary Outcomes (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.

  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)

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

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

• 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)

  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.

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

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

Study Arms (1)

Alternating doxil/Magrath regimen & rituximab/Magrath regimen

EXPERIMENTAL

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; Drug: Regimen B

Interventions

Regimen A DRUG

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

Also known as: 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

Alternating doxil/Magrath regimen & rituximab/Magrath regimen

Regimen B DRUG

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)

Also known as: Rituximab, Ifosfamide, Ifex®, Etoposide, VP-16, VePesid®, VP-16-213, EPEG, epipodophyllotoxin, NSC # 141540, Cytarabine, Cytosar-U, Ara-C, Arabinosyl, cytosine arabinoside

Alternating doxil/Magrath regimen & rituximab/Magrath regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

John H. Stroger Cook County Hospital

Chicago, Illinois, 60612, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Advocate Lutheran General Cancer Care Center

Park Ridge, Illinois, 60068-1174, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

The Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• 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.

  PMID: 24146219 DERIVED

MeSH Terms

Conditions

Lymphoma; Burkitt Lymphoma

Interventions

OOS-A regimen; Rituximab; liposomal doxorubicin; Cyclophosphamide; Vincristine; Methotrexate; merphos; Regimen B; Ifosfamide; Etoposide; Podophyllotoxin; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Aminopterin; Pterins; Pteridines; Oxazines; Heterocyclic Compounds, 1-Ring; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Lignans; Benzyl Compounds; Benzene Derivatives; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Leo Gordon, MD
• Organization: Northwestern University

l-gordon@northwestern.edu

Study Officials

• Leo Gordon, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: February 6, 2007
• Primary Completion: December 3, 2011
• Study Completion: May 28, 2013
• Last Updated: October 15, 2019
• Results First Posted: October 15, 2019

Record last verified: 2019-08

Locations

US (8)