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

July 24, 2014 updated by: Children's Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3H 1P3
        • Montreal Children's Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama Comprehensive Cancer Center
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Arizona Cancer Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital at Stanford
      • San Diego, California, United States, 92123-4282
        • Children's Hospital and Health Center
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital - Atlanta
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital, Chicago
    • Maine
      • Scarborough, Maine, United States, 04074
        • Maine Children's Cancer Program
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Johns Hopkins Oncology Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Children's Hospital of Michigan
    • Missouri
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Hospital
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Hackensack, New Jersey, United States, 07601
        • Tomorrows Children's Institute
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai School of Medicine
    • Texas
      • Dallas, Texas, United States, 75235-9154
        • Simmons Cancer Center - Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Midwest Children's Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Chemo + STEM cell
See detailed description.
Drug: asparaginase
Other Names:
  • E. coli
  • Elspar
  • NSC #109229
Drug: cytarabine
Other Names:
  • Cytosar
  • cytosine arabinoside
  • NSC #063878
  • AraC
Drug: daunorubicin hydrochloride
Other Names:
  • Cerubidine
  • daunomycin
  • DNR
  • NSC #82151
Drug: thioguanine
Other Names:
  • 6-thioguanine
  • 6-TG
  • NSC #000752
Procedure: peripheral blood stem cell transplantation
Biological: filgrastim
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • NSC #614629
  • Neupogen®
  • GCSF
Drug: melphalan
Other Names:
  • Alkeran
  • L-PAM
  • L-phenylalanine mustard
  • L-sarcolysin
  • NSC #008806

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility and toxicity of an intensive regimen that uses timed-sequential therapy
Time Frame: 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.
Length of study
Feasibility and toxicity of a single high dose of melphalan with peripheral stem cell rescue
Time Frame: 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.
Length of study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Make observations regarding PCR evidence of Minimal Residual Disease
Time Frame: Length of study
To make observations regarding PCR evidence of Minimal Residual Disease in patients with relevant specific translocations who obtain a clinical remission.
Length of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Craig A. Hurwitz, MD, Maine Children's Cancer Program at Barbara Bush Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 1999

Primary Completion (Actual)

October 1, 2002

Study Completion (Actual)

March 1, 2007

Study Registration Dates

First Submitted

December 10, 1999

First Submitted That Met QC Criteria

May 19, 2004

First Posted (Estimate)

May 20, 2004

Study Record Updates

Last Update Posted (Estimate)

July 28, 2014

Last Update Submitted That Met QC Criteria

July 24, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9822
  • POG-9822
  • CDR0000067253

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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