Combination Chemotherapy Followed by Melphalan and Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Acute Myeloid Leukemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Chemo + STEM cell See detailed description. |
Biological: filgrastim
Other Names:
Drug: asparaginase
Other Names:
Drug: cytarabine
Other Names:
Drug: daunorubicin hydrochloride
Other Names:
Drug: melphalan
Other Names:
Drug: thioguanine
Other Names:
Procedure: peripheral blood stem cell transplantation
|
Outcome Measures
Primary Outcome Measures
- Feasibility and toxicity of an intensive regimen that uses timed-sequential therapy [Length of study]
To determine the feasibility and toxicity of an intensive regimen that uses timed-sequential therapy as a strategy for both remission induction and consolidation of newly diagnosed children with AML.
- Feasibility and toxicity of a single high dose of melphalan with peripheral stem cell rescue [Length of study]
To test the feasibility and toxicity of a single high dose of melphalan with peripheral stem cell rescue following an intense timed-sequential induction and consolidation.
Secondary Outcome Measures
- Make observations regarding PCR evidence of Minimal Residual Disease [Length of study]
To make observations regarding PCR evidence of Minimal Residual Disease in patients with relevant specific translocations who obtain a clinical remission.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama Comprehensive Cancer Center | Birmingham | Alabama | United States | 35294 |
| 2 | Arizona Cancer Center | Tucson | Arizona | United States | 85724 |
| 3 | University of Arkansas for Medical Sciences | Little Rock | Arkansas | United States | 72205 |
| 4 | Lucile Packard Children's Hospital at Stanford | Palo Alto | California | United States | 94304 |
| 5 | Children's Hospital and Health Center | San Diego | California | United States | 92123-4282 |
| 6 | Nemours Children's Clinic | Jacksonville | Florida | United States | 32207 |
| 7 | Emory University Hospital - Atlanta | Atlanta | Georgia | United States | 30322 |
| 8 | Children's Memorial Hospital, Chicago | Chicago | Illinois | United States | 60614 |
| 9 | Maine Children's Cancer Program | Scarborough | Maine | United States | 04074 |
| 10 | Johns Hopkins Oncology Center | Baltimore | Maryland | United States | 21231 |
| 11 | Massachusetts General Hospital Cancer Center | Boston | Massachusetts | United States | 02114 |
| 12 | Children's Hospital of Michigan | Detroit | Michigan | United States | 48201 |
| 13 | Cardinal Glennon Children's Hospital | Saint Louis | Missouri | United States | 63104 |
| 14 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 15 | Tomorrows Children's Institute | Hackensack | New Jersey | United States | 07601 |
| 16 | Mount Sinai School of Medicine | New York | New York | United States | 10029 |
| 17 | Simmons Cancer Center - Dallas | Dallas | Texas | United States | 75235-9154 |
| 18 | Cook Children's Medical Center - Fort Worth | Fort Worth | Texas | United States | 76104 |
| 19 | Midwest Children's Cancer Center | Milwaukee | Wisconsin | United States | 53226 |
| 20 | Montreal Children's Hospital | Montreal | Quebec | Canada | H3H 1P3 |
Sponsors and Collaborators
- Children's Oncology Group
- National Cancer Institute (NCI)
Investigators
- Study Chair: Craig A. Hurwitz, MD, Maine Children's Cancer Program at Barbara Bush Children's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 9822
- POG-9822
- CDR0000067253