We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is currently recruiting participants.
Verified August 2017 by Children's Oncology Group
Sponsor:
ClinicalTrials.gov Identifier:
NCT02521493
First Posted: August 13, 2015
Last Update Posted: August 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
August 10, 2015
August 13, 2015
August 31, 2017
November 2015
December 2019   (Final data collection date for primary outcome measure)
EFS [ Time Frame: 2 years ]
The Kaplan-Meier method will be used to estimate 2-year EFS from the end of Induction I along with 95% log-minus-log transformed confidence limits separately for high risk and standard risk patients at end of Induction I.
Same as current
Complete list of historical versions of study NCT02521493 on ClinicalTrials.gov Archive Site
Not Provided
  • Average total number of days per patient spent on protocol therapy [ Time Frame: Up to at least 10 years ]
  • Duration of hospitalization [ Time Frame: Up to at least 10 years ]
  • Early death rates [ Time Frame: Up to at least 10 years ]
  • Infection rates [ Time Frame: Up to at least 10 years ]
  • Overall survival [ Time Frame: Up to at least 10 years ]
  • Percentage of patients experiencing grade 3 or higher toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to at least 10 years ]
  • Relapse risk [ Time Frame: Up to at least 10 years ]
  • Time to count recovery [ Time Frame: Up to at least 10 years ]
  • Treatment related mortality [ Time Frame: Up to at least 10 years ]
  • Average total number of days per patient spent on protocol therapy [ Time Frame: 6 months ]
  • Duration of hospitalization [ Time Frame: 6 months ]
  • Early death rates [ Time Frame: 1 month ]
  • Infection rates [ Time Frame: 6 months ]
  • Overall survival [ Time Frame: Up to at least 10 years ]
  • Percentage of patients experiencing grade 3 or higher toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 6 months ]
  • Relapse risk [ Time Frame: Up to at least 10 years ]
  • Time to count recovery [ Time Frame: 6 months ]
  • Treatment related mortality [ Time Frame: 6 months ]
Not Provided
 
Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome
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.

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 determine the extent to which elimination of HD Ara-C from the treatment of standard risk DS AML decreases adverse events and resource utilization.

II. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease in the number of days per patient spent on protocol therapy compared to predecessor study AAML0431.

III. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease in the average number of days of hospitalization per patient compared to predecessor studies AAML0431 and A2971.

IV. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease in the number (per patient) and rate (per duration of treatment) of sterile site infections compared to the predecessor study AAML0431.

V. To determine if elimination of HD Ara-C from treatment of standard risk DS AML results in a significant decrease of resource utilization by AML treatment compared to the predecessor study AAML0431.

VI. 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.

VII. 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):

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 BID 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 BID and etoposide IV over 60-120 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 BID 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 5 years, and then at relapse.

Interventional
Phase 3
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Childhood Acute Myeloid Leukemia
  • Childhood Myelodysplastic Syndrome
  • Cytopenia
  • Down Syndrome
  • Myeloid Leukemia Associated With Down Syndrome
  • Myeloproliferative Neoplasm
  • Drug: Asparaginase
    Given IM or IV
    Other Names:
    • ASP-1
    • Asparaginase II
    • Asparaginase-E.Coli
    • Colaspase
    • Elspar
    • Kidrolase
    • L-Asnase
    • L-ASP
    • L-Asparaginase
    • L-Asparagine Amidohydrolase
    • Laspar
    • Lcf-ASP
    • Leucogen
    • Leunase
    • MK-965
    • Paronal
    • Re-82-TAD-15
    • Serasa
  • Drug: Asparaginase Erwinia chrysanthemi
    Given IM or IV
    Other Names:
    • Crisantaspasum
    • Cristantaspase
    • Erwinase
    • Erwinaze
    • L-asparginase (Erwinia )
  • Drug: Cytarabine
    Given IT and IV
    Other Names:
    • .beta.-Cytosine arabinoside
    • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
    • 1-.beta.-D-Arabinofuranosylcytosine
    • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
    • 1-Beta-D-arabinofuranosylcytosine
    • 1.beta.-D-Arabinofuranosylcytosine
    • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
    • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
    • Alexan
    • Ara-C
    • ARA-cell
    • Arabine
    • Arabinofuranosylcytosine
    • Arabinosylcytosine
    • Aracytidine
    • Aracytin
    • Aracytine
    • Beta-Cytosine Arabinoside
    • CHX-3311
    • Cytarabinum
    • Cytarbel
    • Cytosar
    • Cytosar-U
    • Cytosine Arabinoside
    • Cytosine-.beta.-arabinoside
    • Cytosine-beta-arabinoside
    • Erpalfa
    • Starasid
    • Tarabine PFS
    • U 19920
    • U-19920
    • Udicil
    • WR-28453
  • Drug: Daunorubicin Hydrochloride
    Given IV
    Other Names:
    • Cerubidin
    • Cerubidine
    • Cloridrato de Daunorubicina
    • Daunoblastin
    • Daunoblastina
    • Daunoblastine
    • Daunomycin Hydrochloride
    • Daunomycin, hydrochloride
    • Daunorubicin.HCl
    • Daunorubicini Hydrochloridum
    • FI-6339
    • Ondena
    • RP-13057
    • Rubidomycin Hydrochloride
    • Rubilem
  • Drug: Etoposide
    Given IV
    Other Names:
    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16-213
    • VP-16
    • VP-16-213
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Mitoxantrone Hydrochloride
    Given IV
    Other Names:
    • CL 232315
    • DHAD
    • DHAQ
    • Dihydroxyanthracenedione Dihydrochloride
    • Mitoxantrone Dihydrochloride
    • Mitoxantroni Hydrochloridum
    • Mitozantrone Hydrochloride
    • Mitroxone
    • Neotalem
    • Novantrone
    • Onkotrone
    • Pralifan
  • Drug: Thioguanine
    Given PO
    Other Names:
    • 2-Amino 6MP
    • 2-Amino-1,7-dihydro-6H-purine-6-thione
    • 2-Amino-6-mercaptopurine
    • 2-Amino-6-purinethiol
    • 2-Aminopurin-6-thiol
    • 2-Aminopurine-6(1H)-thione
    • 2-Aminopurine-6-thiol
    • 2-Mercapto-6-aminopurine
    • 6-Amino-2-mercaptopurine
    • 6-Mercapto-2-aminopurine
    • 6-Mercaptoguanine
    • 6-TG
    • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
    • BW 5071
    • Lanvis
    • Tabloid
    • Tioguanin
    • Tioguanine
    • Wellcome U3B
    • WR-1141
    • X 27
  • Experimental: Arm A (standard risk)

    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.

    Interventions:
    • Drug: Cytarabine
    • Drug: Daunorubicin Hydrochloride
    • Drug: Etoposide
    • Other: Laboratory Biomarker Analysis
    • Drug: Thioguanine
  • Experimental: Arm B (high risk)

    INDUCTION II: Patients receive high dose cytarabine IV over 1-3 hours BID 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 BID and etoposide IV over 60-120 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 BID on days 1, 2, 8, and 9. Patients also receive asparaginase or asparaginase Erwinia chrysanthemi IM or IV over 30 minutes on days 2 and 9. Intensification II continues for a minimum of 28 days.

    Interventions:
    • Drug: Asparaginase
    • Drug: Asparaginase Erwinia chrysanthemi
    • Drug: Cytarabine
    • Other: Laboratory Biomarker Analysis
    • Drug: Mitoxantrone Hydrochloride
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
256
Not Provided
December 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization [FISH])
  • Patients with previously untreated de novo AML who meet the criteria for AML with >= 20% bone marrow blasts as set out in the World Health Organization (WHO) Myeloid Neoplasm classification
  • Patients with cytopenias and/or bone marrow blasts who do not meet the criteria for the diagnosis of AML (WHO Myeloid Neoplasm classification) because of < 20% marrow blasts are eligible if they meet the criteria for a diagnosis of myelodysplastic syndrome (MDS)
  • Patients with a history of transient myeloproliferative disorder (which may or may not have required chemotherapy intervention), who:

    • Are > 8 weeks since resolution of transient myeloproliferative disease (TMD) with >= 5% blasts, OR
    • Patients sho have an increasing blast count (>= 5%) in serial bone marrow aspirates performed at least 4 weeks apart
  • Children who have previously received chemotherapy, radiation therapy or any anti-leukemic therapy are not eligible for this protocol, with the exception of cytarabine for the treatment of TMD
  • There are no minimal organ function requirements for enrollment on this study

    • Note: Previous cardiac repair with sufficient cardiac function is not an exclusion criteria
  • Each patient's parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human subjects research must be met

Exclusion Criteria:

  • Patients with promyelocytic leukemia (French-American-British [FAB] M3)
  • Prior therapy

    • Patients =< 30 days from the last dose of cytarabine used for treatment of TMD
Sexes Eligible for Study: All
91 Days to 3 Years   (Child)
No
United States
 
 
NCT02521493
AAML1531
NCI-2015-00324 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AAML1531 ( Other Identifier: Children's Oncology Group )
AAML1531 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
Not Provided
Not Provided
Not Provided
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Jason Berman Children's Oncology Group
Children's Oncology Group
August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP