Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes
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|ClinicalTrials.gov Identifier: NCT00369317|
Recruitment Status : Completed
First Posted : August 29, 2006
Results First Posted : January 13, 2015
Last Update Posted : January 28, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Childhood Acute Basophilic Leukemia Childhood Acute Eosinophilic Leukemia Childhood Acute Erythroleukemia (M6) Childhood Acute Megakaryocytic Leukemia (M7) Childhood Acute Minimally Differentiated Myeloid Leukemia (M0) Childhood Acute Monoblastic Leukemia (M5a) Childhood Acute Monocytic Leukemia (M5b) Childhood Acute Myeloblastic Leukemia With Maturation (M2) Childhood Acute Myeloblastic Leukemia Without Maturation (M1) Childhood Acute Myelomonocytic Leukemia (M4) Childhood Myelodysplastic Syndromes de Novo Myelodysplastic Syndromes Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies||Drug: asparaginase Drug: daunorubicin hydrochloride Drug: cytarabine Drug: thioguanine Drug: etoposide Other: laboratory biomarker analysis||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||205 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Treatment of Down Syndrome Children With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Under the Age of 4 Years|
|Study Start Date :||March 2007|
|Actual Primary Completion Date :||December 1, 2013|
|Actual Study Completion Date :||December 31, 2021|
Experimental: Treatment (combination chemotherapy)
INDUCTION THERAPY COURSE I: Patients receive cytarabine IT on day 1 and cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV continuously, and oral thioguanine BID on days 1-4. COURSE II: Patients receive high-dose cytarabine IV over 3 hours BID on days 1, 2, 8, and 9 and asparaginase (IM) on days 2 and 9.
COURSE III: Patients receive treatment as in course I. COURSE IV: Patients receive cytarabine IV, daunorubicin hydrochloride IV, and oral thioguanine as in course I
INTENSIFICATION THERAPY: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Drug: daunorubicin hydrochloride
Given IV or IT
Other Name: 6-TG
Other: laboratory biomarker analysis
- Event-free Survival (EFS) at 3 Years [ Time Frame: Time from study entry to induction failure, relapse, or death assessed at 3 years. ]
- Overall Survival (OS) at 3 Years [ Time Frame: Time from study entry to death, assessed at 3 years. ]
- Induction Remission Rate [ Time Frame: End of induction therapy (day 112) ]Proportion of participants with a remission after four courses of Induction therapy.
- Percentage of Patients Experiencing Grade 3 or 4 Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: From the beginning of induction therapy to the end of intensification therapy ]Proportion of participants with at least one grade 3 or higher adverse event during therapy.
- Prevalence of Leukemia Phenotype of DS Patients < 4 Years of Age at Diagnosis by Flow Cytometry [ Time Frame: At the start of therapy ]Proportion of participants having megakaryoblastic subtype (AMkL) phenotype among patients with phenotype data available.
- Prevalence of of GATA1 Mutations of DS Patients < 4 Years of Age at Diagnosis [ Time Frame: At baseline and at the end of therapy (intensification) or disease relapse ]Proportion of participants having GATA1 mutation among patients with phenotype data available.
- Proportions of Patients in Morphologic Remission With Positive MRD by Flow Cytometry [ Time Frame: After Induction I therapy (day 28 from start of therapy) ]Proportion of participants in complete remission by morphology and with positive MRD by flow cytometry among patients having evaluable remission and MRD assessment.
- Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program [ Time Frame: Days 1, 2, 8, and 9 of induction II ]Mean and standard deviation of peak plasma concentration. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only.
- Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program [ Time Frame: Days 1, 2, 8, and 9 of induction II ]Mean and standard deviation of area under the concentration time curve. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only.
- Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program [ Time Frame: Days 1, 2, 8, and 9 of induction II ]Mean and standard deviation of half-life of elimination. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only.
- Gene Expression Profiles by Microarrays [ Time Frame: At baseline and at the time of relapse (if available) ]A hierarchical clustering algorithm is used to assemble the genes into a dendrogram or tree structure with branches containing genes with similar patterns of expression. This ordered representation can be graphically displayed with colors that reflect the qualitative and quantitative relationships of the expressed genes.
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|Ages Eligible for Study:||up to 4 Years (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Diagnosis DS or DS mosaicism by karyotype or chromosomal analysis
Diagnosis of myelodysplastic syndromes (MDS) with < 30% blasts or acute myeloid leukemia (AML)
- Newly diagnosed disease
Patients with a history of transient myeloproliferative disorder (TMD) are eligible provided the patient is diagnosed with AML or MDS at > 90 days of age AND meets either of the following criteria:
- At least 30% blasts in the bone marrow regardless of time since resolution of TMD
- More than 8 weeks since resolution of TMD with ≥ 5% blasts in the bone marrow
- Immunophenotype required for study entry
- No promyelocytic leukemia
- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST or ALT < 2.5 times ULN
Creatinine adjusted according to age as follows:
- No greater than 0.4 mg/dL (≤ 5 months)
- No greater than 0.5 mg/dL (6 months -11 months)
- No greater than 0.6 mg/dL (1 year-23 months)
- No greater than 0.8 mg/dL (2 years-5 years)
- No greater than 1.0 mg/dL (6 years-9 years)
- No greater than 1.2 mg/dL (10 years-12 years)
- No greater than 1.4 mg/dL (13 years and over [female])
- No greater than 1.5 mg/dL (13 years to 15 years [male])
- No greater than 1.7 mg/dL (16 years and over [male])
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
- No evidence of dyspnea at rest
- No exercise intolerance
- Pulse oximetry > 94%
No prior chemotherapy, radiotherapy, or any antileukemic therapy
- Intrathecal cytarabine therapy given at diagnosis allowed
- Prior therapy for TMD allowed
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00369317
|Principal Investigator:||Jeffrey Taub, MD||Children's Oncology Group|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Children's Oncology Group|
|Other Study ID Numbers:||
NCI-2009-00318 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000492776 ( Other Identifier: Clinical Trials.gov )
COG-AAML0431 ( Other Identifier: Children's Oncology Group )
AAML0431 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
|First Posted:||August 29, 2006 Key Record Dates|
|Results First Posted:||January 13, 2015|
|Last Update Posted:||January 28, 2022|
|Last Verified:||March 2021|
Leukemia, Myeloid, Acute
Leukemia, Monocytic, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Erythroblastic, Acute
Leukemia, Basophilic, Acute
Leukemia, Eosinophilic, Acute
Leukemia, Megakaryoblastic, Acute
Neoplasms by Histologic Type
Bone Marrow Diseases
Nervous System Diseases