Clinical trial NCT00002494: Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma or Acute Lymphocytic Leukemia
Official title: HIGH INTENSITY, BRIEF DURATION CHEMOTHERAPY FOR DIFFUSE SMALL NONCLEAVED CELL LYMPHOMA AND THE L-3 SUBTYPE OF ALL: A PILOT STUDY OF A MULTIDRUG REGIMEN
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 II 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: 2004-04-06
Enrollment: 134
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and alternating regimens of chemotherapy in treating patients who have non-Hodgkin's lymphoma or acute lymphocytic leukemia.

Detailed description: OBJECTIVES: I. Determine the response rate and disease free survival of HIV seronegative patients with diffuse small noncleaved cell lymphoma or L3 acute lymphocytic leukemia when treated with high intensity, brief duration combination chemotherapy: alternating courses of ifosfamide/cytarabine/etoposide and cyclophosphamide/doxorubicin, each with methotrexate/vincristine/dexamethasone. II. Determine the toxicity of these regimens in HIV negative patients.

OUTLINE: Patients are stratified by participating institution and disease type (diffuse small noncleaved cell lymphoma vs L3 ALL). Patients receive cyclophosphamide IV over 5-10 minutes on days 1 through 5 and oral prednisone on days 1 through 7, followed by alternating courses of: 2) ifosfamide IV over 1 hour on days 8 through 12, methotrexate IV over 24 hours on day 8; leucovorin calcium IV over 36 hours after initiation of methotrexate, then IV (or orally as tolerated, after the first 24 hours) every 6 hours until the serum methotrexate level is below 5 x 10 to the minus eighth M; vincristine IV on day 8; cytarabine IV over 48 hours and etoposide IV over 60 minutes on days 11 and 12; and oral dexamethasone on days 8 through 12, plus triple intrathecal therapy (TIT) with methotrexate, cytarabine, and hydrocortisone on days 8 and 12, and 3) cyclophosphamide IV over 5-10 minutes on days 29 through 33; methotrexate IV over 24 hours and vincristine IV on day 29; leucovorin calcium IV over 36 hours after initiation of methotrexate, then IV (or orally as tolerated, after the first 24 hours) every 6 hours until the serum methotrexate level is below 5 x 10 to the minus eighth M; doxorubicin IV on days 32 and 33; and oral dexamethasone on days 29 through 33, plus TIT on day 29, with doses as above. Patients with CNS disease at diagnosis continue TIT once weekly until the CSF clears, then weekly for 4 more weeks. TIT must be completed prior to initiation of radiotherapy. All patients must complete at least the first 3 courses of chemotherapy. Courses 2 and 3 each repeat 3 times in the absence of disease progression or unacceptable toxicity. On days 134-139, patients who have had prior bone marrow involvement receive cranial radiation therapy. Patients who achieve less than a complete response and who have an HLA-matched sibling should undergo allogeneic bone marrow transplant on protocol CLB-9113. Patients are followed monthly for 6 months, every 2 months for 18 months, every 6 months for 2 years, and thereafter for survival.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically documented diffuse small noncleaved cell lymphoma (category J by IWF) of any stage Nodal or abdominal masses with less than 25% lymphoblasts in marrow are defined as lymphoma OR Histologically documented L3 acute lymphocytic leukemia (ALL) Greater than 25% lymphoblasts in marrow is defined as ALL, regardless of presence of bulky nodal disease Lymphoma requirements include: Documentation of lymphadenopathy, splenomegaly, or hepatomegaly, presence or absence of abdominal masses, and presence or absence of B symptoms Measurable disease other than ascites and pleural effusions, bony disease, and CNS lesions Bidimensionally measurable mass on physical exam, x-ray, or CT, or MRI OR Clearly defined hepatic mass greater than 3.5 cm on CT, MRI, or ultrasound considered to represent lymphoma OR Histologically documented hepatic lymphoma with the liver extending more than 5 cm below the costal margin on quiet respiration ALL requirements include: Documentation of monoclonal surface immunoglobulin by surface immunophenotyping Lymph node biopsy strongly recommended for patients with obvious marrow involvement Disease labeled L3 but also manifested by lymphadenopathy must be evaluated as is lymphoma (see above)

PATIENT CHARACTERISTICS: Age: 15 and over Performance status: Any status Life expectancy: At least 2 years Hematopoietic: Not specified Hepatic: Bilirubin no greater than 1.5 times normal (unless further elevation is directly attributable to malignancy) Renal: Creatinine no greater than 1.5 times normal (unless further elevation is directly attributable to malignancy) Cardiovascular: No uncontrolled or severe cardiovascular disease, e.g.: No myocardial infarction within the past 6 months No congestive heart failure Other: HIV negative No active, uncontrolled bacterial, viral, or fungal infection No active, uncontrolled duodenal ulcer No other serious medical illness No serious psychiatric condition that would preclude informed consent or protocol compliance No second malignancy within 5 years except: Curatively treated carcinoma in situ of the cervix Curatively treated basal cell carcinoma Not pregnant Effective contraception required of fertile patients

PRIOR CONCURRENT THERAPY: Biologic: No concurrent growth factors Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: No concurrent palliative radiotherapy Surgery: Not specified Other: No prior therapy

Primary outcomes:
measure: complete response
timeFrame: up to 5 years post-transplant
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Wilmington
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: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Baltimore
country: United States
facility: Marlene & Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
state: North Carolina
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Memphis
country: United States
facility: University of Tennessee, Memphis Cancer Center
state: Tennessee
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
Study officials:
affiliation: Central Maryland Oncology Center
name: Edward Lee, MD
role: STUDY_CHAIR
References:
citation: Rizzieri DA, Johnson JL, Niedzwiecki D, Lee EJ, Vardiman JW, Powell BL, Barcos M, Bloomfield CD, Schiffer CA, Peterson BA, Canellos GP, Larson RA. Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251. Cancer. 2004 Apr 1;100(7):1438-48. doi: 10.1002/cncr.20143.
citation: Lee EJ, Petroni GR, Schiffer CA, Freter CE, Johnson JL, Barcos M, Frizzera G, Bloomfield CD, Peterson BA. Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol. 2001 Oct 15;19(20):4014-22. doi: 10.1200/JCO.2001.19.20.4014.