Combination Chemotherapy Followed by Melphalan and Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Acute Myeloid Leukemia

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004056
• Other study ID #: 9822
• Secondary ID: POG-9822CDR00000
• Status: Completed
• Phase: Phase 1
• First received: December 10, 1999
• Last updated: July 24, 2014
• Start date: October 1999
• Est. completion date: March 2007

Study information

• Verified date: July 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: March 2007
• Est. primary completion date: October 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid, Acute

Intervention

Biological:
• filgrastim

Drug:
• asparaginase

• cytarabine

• daunorubicin hydrochloride

• melphalan

• thioguanine

Procedure:
• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
Canada	Montreal Children's Hospital	Montreal	Quebec
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Tomorrows Children's Institute	Hackensack	New Jersey
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Mount Sinai School of Medicine	New York	New York
United States	Lucile Packard Children's Hospital at Stanford	Palo Alto	California
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Children's Hospital and Health Center	San Diego	California
United States	Maine Children's Cancer Program	Scarborough	Maine
United States	Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility and toxicity of an intensive regimen that uses timed-sequential therapy	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.	Length of study	Yes
Primary	Feasibility and toxicity of a single high dose of melphalan with peripheral stem cell rescue	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.	Length of study	Yes
Secondary	Make observations regarding PCR evidence of Minimal Residual Disease	To make observations regarding PCR evidence of Minimal Residual Disease in patients with relevant specific translocations who obtain a clinical remission.	Length of study	No