Last updated on July 2019

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome


Brief description of study

This phase III trial studies response-based chemotherapy in treating newly diagnosed acute myeloid leukemia or myelodysplastic syndrome in younger patients with Down syndrome. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Response-based chemotherapy separates patients into different risk groups and treats them according to how they respond to the first course of treatment (Induction I). Response-based treatment may be effective in treating acute myeloid leukemia or myelodysplastic syndrome in younger patients with Down syndrome while reducing the side effects.

Detailed Study Description

PRIMARY OBJECTIVES:

I. To determine the 2-year event-free-survival (EFS) for children with standard risk Down syndrome (DS) acute myeloid leukemia (AML) (minimal residual disease [MRD]-negative after one cycle of induction therapy) after elimination of high dose (HD) Ara-C (cytarabine) from the treatment regimen.

II. To determine the 2-year EFS for children with high risk DS AML (MRD-positive after one cycle of induction therapy) after intensification of treatment equivalent to that used for high risk AML in children without DS.

EXPLORATORY OBJECTIVES:

I. To compare the feasibility and analytical characteristics of flow cytometry, polymerase chain reaction (PCR) and targeted error-corrected sequencing of GATA binding protein 1 (globin transcription factor 1) (GATA1) mutations as methods to detect MRD in DS AML.

II. To establish a DS AML cell bank of viably frozen bone marrow samples collected at the end of induction and corresponding non-tumor deoxyribonucleic acid (DNA) samples collected at end of Induction 1.

OUTLINE

INDUCTION I: Patients receive cytarabine intrathecally (IT) on day 1 and intravenously (IV) continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine orally (PO) twice daily (BID) on days 1-4. Induction I continues for a minimum of 28 days.

Patients are assigned to 1 of 2 treatment arms based on their MRD status after completion of Induction I.

ARM A (STANDARD RISK) (Closed to accrual and treatment with amendment #4A 01/07/2019):

INDUCTION II: Patients receive cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine PO BID on days 1-4. Induction II continues for a minimum of 28 days.

INDUCTION III: Patients receive cytarabine, daunorubicin hydrochloride, and thioguanine as in Induction II. Induction III continues for a minimum of 28 days.

INTENSIFICATION I: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 60-120 minutes on days 1-3. Intensification I continues for a minimum of 28 days.

INTENSIFICATION II: Patients receive cytarabine and etoposide as in Intensification I. Intensification II continues for a minimum of 28 days.

ARM B (HIGH RISK):

INDUCTION II: Patients receive high dose cytarabine IV over 1-3 hours every 12 (Q12) hours on days 1-4 and mitoxantrone hydrochloride IV over 15-30 minutes on days 3-6. Induction II continues for a minimum of 28 days.

INTENSIFICATION I: Patients receive high dose cytarabine IV over 1-3 hours Q12 hours and etoposide IV over 90-120 minutes on days 1-5. Intensification I continues for a minimum of 28 days.

INTENSIFICATION II: Patients receive high dose cytarabine IV over 3 hours Q12 hours on days 1, 2, 8, and 9. Patients also receive asparaginase or asparaginase Erwinia chrysanthemi (E. carotovora) intramuscularly (IM) or IV over 30 minutes on days 2 and 9. Intensification II continues for a minimum of 28 days.

After completion of study treatment, patients are followed up at 1 month, monthly for 12 months, every 3 months for 12 months, every 6 months for 3 years, annually for 10 years, and then at relapse.

Clinical Study Identifier: NCT02521493

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Cleveland Clinic Foundation

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Children's Hospital of Alabama

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Arkansas Children's Hospital

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Children's Hospital Los Angeles

Los Angeles, CA United States
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Yale University

New Haven, CT United States
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AdventHealth Orlando

Orlando, FL United States
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Nemours Children's Hospital

Orlando, FL United States
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Johns Hopkins All Children's Hospital

Saint Petersburg, FL United States
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Blank Children's Hospital

Des Moines, IA United States
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Norton Children's Hospital

Louisville, KY United States
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C S Mott Children's Hospital

Ann Arbor, MI United States
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Bronson Methodist Hospital

Kalamazoo, MI United States
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Columbia Regional

Columbia, MO United States
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East Carolina University

Greenville, NC United States
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Geisinger Medical Center

Danville, PA United States
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T C Thompson Children's Hospital

Chattanooga, TN United States
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Driscoll Children's Hospital

Corpus Christi, TX United States
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Cook Children's Medical Center

Fort Worth, TX United States
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University Medical Center

Lubbock, TX United States
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Primary Children's Hospital

Salt Lake City, UT United States
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Seattle Children's Hospital

Seattle, WA United States
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Riley Hospital for Children

Indianapolis, IN United States
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Mercy Hospital Saint Louis

Saint Louis, MO United States
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Phoenix Childrens Hospital

Phoenix, AZ United States
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Cedars Sinai Medical Center

Los Angeles, CA United States
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UCSF Medical Center-Mission Bay

San Francisco, CA United States
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University of Illinois

Chicago, IL United States
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Hurley Medical Center

Flint, MI United States
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Mayo Clinic

Rochester, MN United States
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Morristown Medical Center

Morristown, NJ United States
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Albany Medical Center

Albany, NY United States
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NYU Winthrop Hospital

Mineola, NY United States
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University of Rochester

Rochester, NY United States
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New York Medical College

Valhalla, NY United States
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Rhode Island Hospital

Providence, RI United States
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John Hunter Children's Hospital

Hunter Regional Mail Centre, Australia
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Christchurch Hospital

Christchurch, New Zealand
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Broward Health Medical Center

Fort Lauderdale, FL United States
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Recruitment Status: Open


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