Clinical trial NCT00004056: Combination Chemotherapy Followed by Melphalan and Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Acute Myeloid Leukemia
Official title: Treatment of Newly Diagnosed Childhood AML Using a Timed-Sequential Remission Induction and Consolidation Followed by Single Dose Melphalan With Peripheral Stem Cell Rescue: A POG Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Keywords: untreated childhood acute myeloid leukemia and other myeloid malignancies
childhood acute monoblastic leukemia and acute monocytic leukemia (M5)
childhood acute myeloblastic leukemia without maturation (M1)
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute myelomonocytic leukemia (M4)
childhood acute erythroleukemia (M6)
childhood acute megakaryocytic leukemia (M7)
childhood acute minimally differentiated myeloid leukemia (M0)
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-05-20
Enrollment: 35
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
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. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy followed by melphalan and peripheral stem cell transplantation in treating children who have newly diagnosed acute myeloid leukemia that has not been treated previously.

Detailed description: OBJECTIVES: I. Determine the feasibility and toxicity of timed sequential remission induction and consolidation in children with newly diagnosed acute myeloid leukemia. II. Determine the feasibility and toxicity of a single high dose of melphalan with peripheral blood stem cell rescue following an intense timed sequential induction and consolidation in these children.

OUTLINE: This is a multicenter study. Remission induction: Patients receive daunorubicin IV over 15 minutes on days 1-3, cytarabine IV continuously on days 1-7, oral thioguanine daily on days 1-7, and cytarabine intrathecally (IT) on day 1. Cytarabine IV over 3 hours is administered every 12 hours on days 10-12. Filgrastim (G-CSF) is administered IV or subcutaneously (SQ) beginning on day 13 and continuing until blood counts recover. On approximately day 28, patients undergo a bone marrow aspirate and biopsy to assess response. Patients who have attained an M1 or M2a status proceed to consolidation or, if a 5/5 or 6/6 HLA matched sibling donor is available, proceed to allogeneic bone marrow transplantation. Patients with greater than 25% blasts go off study. Consolidation 1: Patients receive daunorubicin IV over 15 minutes on days 1 and 2, cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9, and asparaginase on days 2 and 9. G-CSF IV or SQ begins on day 10 and continues until blood counts recover. Consolidation 2: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5. G-CSF IV or SQ begins on day 6 and continues until blood counts recover. Peripheral blood stem cells (PBSC) are collected after the second course of consolidation. Consolidation 3: Treatment is repeated as in consolidation 1. Patients who remain in morphologic remission after consolidation 3 proceed with therapy. Patients receive melphalan IV over 30 minutes on day -2, then PBSC are reinfused on day 0. G-CSF IV or SQ begins on day 1 and continues until blood counts recover. Patients are followed every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 20-30 patients will be accrued for this study within 8 months.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically proven, previously untreated primary acute myeloid leukemia (AML) Isolated granulocytic sarcoma (myeloblastoma) allowed Patients with cytopenias and bone marrow blasts greater than 5% but less than 30% eligible only if there is karyotypic abnormality characteristic of de novo AML (t(8;21), inv16, t(9;11), etc.) OR unequivocal presence of megakaryoblasts No acute promyelocytic leukemia (M3) No Down syndrome

PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 3 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL Uric acid no greater than 8.0 mg/dL Cardiovascular: Cardiac function normal by echocardiogram Pulmonary: No uncontrolled, life threatening pneumonia Other: No uncontrolled, life threatening sepsis or meningitis Not pregnant Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: No prior therapy

Primary outcomes:
measure: Feasibility and toxicity of an intensive regimen that uses timed-sequential therapy
timeFrame: Length of study
measure: Feasibility and toxicity of a single high dose of melphalan with peripheral stem cell rescue
timeFrame: Length of study
Secondary outcomes:
measure: Make observations regarding PCR evidence of Minimal Residual Disease
timeFrame: Length of study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital at Stanford
state: California
city: San Diego
country: United States
facility: Children's Hospital and Health Center
state: California
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital, Chicago
state: Illinois
city: Scarborough
country: United States
facility: Maine Children's Cancer Program
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins Oncology Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Hospital
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: Tomorrows Children's Institute
state: New Jersey
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Dallas
country: United States
facility: Simmons Cancer Center - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
Study officials:
affiliation: Maine Children's Cancer Program at Barbara Bush Children's Hospital
name: Craig A. Hurwitz, MD
role: STUDY_CHAIR
References:
citation: Hurwitz CA, Chang M, Graham M, et al.: Timed-sequential remission induction and intensification followed by stem cell rescue for childhood AML -a POG pilot study. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1553, 2002.