Clinical trial NCT00039130: Rituximab, Chemotherapy, and Filgrastim in Treating Patients With Burkitt's Lymphoma or Burkitt's Leukemia
Official title: Phase II Study Of Rituximab And Short Duration, High Intensity Chemotherapy With G-CSF Support In Previously Untreated Patients With Burkitt Lymphoma/Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Keywords: untreated adult acute lymphoblastic leukemia
L3 adult acute lymphoblastic leukemia
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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 105
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the numbers of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Combining chemotherapy with rituximab and filgrastim may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with chemotherapy and filgrastim in treating patients who have Burkitt's lymphoma or Burkitt's leukemia.

Detailed description: OBJECTIVES:

* Determine the complete response rate in patients with previously untreated Burkitt's lymphoma or Burkitt's leukemia treated with rituximab and high-intensity chemotherapy with filgrastim (G-CSF) support.
* Determine the progression-free and overall survival of patients treated with this regimen.
* Determine the feasibility and toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (leukemia vs lymphoma).

* Course 1: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5 and oral prednisone on days 1-7. Allopurinol PO will be given on days 1-14.
* Courses 2, 4, and 6: Patients receive ifosfamide IV over 1 hour daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV over 15 minutes every 6 hours on day 2; cytarabine IV over 2 hours on days 4 and 5 and etoposide IV over 1 hour daily on days 4 and 5; oral dexamethasone daily on days 1-5; and methotrexate and cytarabine intrathecally (IT) on day 1. During course 2, patients receive rituximab IV over 1-4 hours on days 8, 10, and 12. During courses 4 and 6, patients receive rituximab IV over 1 hour on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 7 and continuing until blood counts recover.
* Courses 3, 5, and 7: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV every 6 hours on day 2; doxorubicin IV daily on days 4 and 5; oral dexamethasone daily on days 1-5; methotrexate and cytarabine IT on day 1; and rituximab IV over 1 hour on day 8. Patients also receive G-CSF as in courses 2, 4, and 6. After course 3, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per stratum) will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically, cytogenetically, or immunophenotypically confirmed Burkitt's leukemia or Burkitt's or Burkitt-like lymphoma

  * L3 morphology surface IgG expression
  * Cytogenetic evidence for t(8;14), t(8;22), or t(2;8)
* Previously untreated disease except hydroxyurea for leukocytosis
* CNS involvement allowed
* Patients with Burkitt's leukemia or Burkitt's lymphoma with bone marrow involvement must also be enrolled on CALGB-8461
* Patients with Burkitt's leukemia must also be enrolled on CALGB-9665

PATIENT CHARACTERISTICS:

Age:

* 16 and over

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)

Renal:

* Creatinine no greater than 1.5 times ULN

Other:

* HIV negative
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent interleukin-11

Chemotherapy:

* See Disease Characteristics
* No other concurrent chemotherapy

Endocrine therapy:

* No concurrent hormonal therapy except for non-disease-related conditions (e.g., insulin for diabetes)
* No concurrent steroids except for adrenal failure

Radiotherapy:

* No concurrent palliative radiotherapy except whole-brain irradiation for documented CNS disease

Primary outcomes:
measure: Complete Response Rate
timeFrame: 6 months
Secondary outcomes:
measure: 2 Year Event Free Survival
timeFrame: 2 years
measure: 2 Year Overall Survival
timeFrame: 2 years
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Naval Medical Center - San Diego
state: California
city: Lewes
country: United States
facility: Tunnell Cancer Center at Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Bettendorf
country: United States
facility: Hematology Oncology Associates of the Quad Cities
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Elkton
country: United States
facility: Union Hospital Cancer Program at Union Hospital
state: Maryland
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Lake Success
country: United States
facility: Monter Cancer Center of the North Shore-LIJ Health System
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: Don Monti Comprehensive Cancer Center at North Shore University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital Comprehensive Cancer Center
state: Rhode Island
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Berlin
country: United States
facility: Mountainview Medical
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
Study officials:
affiliation: Duke University Medical Center Bone Marrow Transplant
name: David Rizzieri, MD
role: STUDY_CHAIR
References:
citation: Rizzieri DA, Johnson JL, Byrd JC, Lozanski G, Blum KA, Powell BL, Shea TC, Nattam S, Hoke E, Cheson BD, Larson RA; Alliance for Clinical Trials In Oncology (ACTION). Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002. Br J Haematol. 2014 Apr;165(1):102-11. doi: 10.1111/bjh.12736. Epub 2014 Jan 15.