Trial record 2 of 57 for:    Open Studies | "Down Syndrome"

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2015 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT02521493
First received: August 10, 2015
Last updated: August 12, 2015
Last verified: August 2015
  Purpose

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.


Condition Intervention Phase
Childhood Acute Myeloid Leukemia
Childhood Myelodysplastic Syndrome
de Novo Myelodysplastic Syndrome
Down Syndrome
Myeloid Leukemia Associated With Down Syndrome
Drug: Asparaginase
Drug: Asparaginase Erwinia chrysanthemi
Drug: Cytarabine
Drug: Daunorubicin Hydrochloride
Drug: Etoposide
Other: Laboratory Biomarker Analysis
Drug: Mitoxantrone Hydrochloride
Drug: Thioguanine
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • EFS [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Average total number of days per patient spent on protocol therapy [ Time Frame: Up to at least 10 years ] [ Designated as safety issue: No ]
  • Duration of hospitalization [ Time Frame: Up to at least 10 years ] [ Designated as safety issue: No ]
  • Early death rates [ Time Frame: Up to at least 10 years ] [ Designated as safety issue: No ]
  • Infection rates [ Time Frame: Up to at least 10 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to at least 10 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Relapse risk [ Time Frame: Up to at least 10 years ] [ Designated as safety issue: No ]
  • Time to count recovery [ Time Frame: Up to at least 10 years ] [ Designated as safety issue: No ]
  • Treatment related mortality [ Time Frame: Up to at least 10 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 256
Study Start Date: August 2015
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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-Arabinofuranosylcytosine
  • 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
  • CYTARABINE
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosar-U
  • Cytosine 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 HYDROCHLORIDE
  • Daunorubicin.HCl
  • Daunorubicini Hydrochloridum
  • FI-6339
  • Ondena
  • RP-13057
  • Rubidomycin
  • Rubidomycin Hydrochloride
  • Rubilem
Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • ETOPOSIDE
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
Other: Laboratory Biomarker Analysis
Correlative studies
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
  • THIOGUANINE
  • Tioguanin
  • Tioguanine
  • Wellcome U3B
  • WR-1141
  • X 27
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 1-3 hours BID on days 1, 2, 8, and 9. Patients also receive asparaginase or asparaginase Erwinia chrysanthemi IM on days 2 and 9. Intensification II continues for a minimum of 28 days.

Drug: Asparaginase
Given IM
Other Names:
  • ASP-1
  • ASPARAGINASE
  • 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
Other Names:
  • ASPARAGINASE ERWINIA CHRYSANTHEMI
  • 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-Arabinofuranosylcytosine
  • 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
  • CYTARABINE
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosar-U
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
  • CL 232315
  • DHAD
  • DHAQ
  • Dihydroxyanthracenedione Dihydrochloride
  • Mitoxantrone Dihydrochloride
  • MITOXANTRONE HYDROCHLORIDE
  • Mitoxantroni Hydrochloridum
  • Mitozantrone Hydrochloride
  • Mitroxone
  • Neotalem
  • Novantrone
  • Onkotrone
  • Pralifan

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   91 Days to 3 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 > 90 days old at diagnosis of AML/MDS
    • > 30 days from the last dose of cytarabine
    • Have >= 20% blasts in the bone marrow, regardless of the interval of time since TMD resolution, or
    • Are > 8 weeks since TMD resolution with >= 5% bone marrow (BM) blasts, and,
    • Who have an increasing blast count in serial BM aspirates performed at least 4 weeks apart
  • With the exception of TMD as outlined and corticosteroids, children who have previously received chemotherapy, radiation therapy or any anti-leukemic therapy are not eligible for this protocol
  • 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) are not eligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02521493

Locations
United States, Pennsylvania
Children's Oncology Group Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jason N. Berman    902-470-8048    jason.berman@iwk.nshealth.ca   
Principal Investigator: Jason N. Berman         
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Jason Berman Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT02521493     History of Changes
Other Study ID Numbers: AAML1531, NCI-2015-00324, AAML1531, AAML1531, U10CA180886
Study First Received: August 10, 2015
Last Updated: August 12, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Down Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Syndrome
Abnormalities, Multiple
Bone Marrow Diseases
Chromosome Disorders
Congenital Abnormalities
Disease
Genetic Diseases, Inborn
Hematologic Diseases
Intellectual Disability
Neoplasms
Neoplasms by Histologic Type
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Pathologic Processes
Precancerous Conditions
2-Aminopurine
6-Mercaptopurine
Asparaginase
Cytarabine
Daunorubicin
Etoposide
Etoposide phosphate
Mitoxantrone

ClinicalTrials.gov processed this record on September 02, 2015