Ignite Creation Date:
2024-05-05 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00369317
Status:
COMPLETED
Last Update Posted:
2022-01-28
First Post:
2006-08-24
Brief Title:
Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
The Treatment of Down Syndrome Children With Acute Myeloid Leukemia AML and Myelodysplastic Syndromes MDS Under the Age of 4 Years
Status:
COMPLETED
Status Verified Date:
2021-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial is studying how well combination chemotherapy works in treating young patients with Down syndrome and acute myeloid leukemia or myelodysplastic syndromes Drugs used in chemotherapy work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing Giving more than one drug combination chemotherapy may kill more cancer cells
Detailed Description:
PRIMARY OBJECTIVES
I Determine the event-free survival EFS and overall survival rates in pediatric patients with Down syndrome DS and acute myeloid leukemia AML or myelodysplastic syndromes MDS treated with induction therapy comprising cytarabine daunorubicin hydrochloride thioguanine and asparaginase followed by intensification therapy comprising cytarabine and etoposide
II Determine if the EFS rate in these patients can be increased with an intensified course of cytarabine therapy during induction therapy compared to the EFS rate of patients in protocol COG-A2971
III Determine if the number of intrathecal chemotherapy treatments can be reduced in these patients
IV Determine if the total cumulative anthracycline dose can be reduced in these patients
SECONDARY OBJECTIVES
I Determine the type and degree of treatment-related toxicity in these patients
II Determine the prevalence of leukemia phenotype and globin transcription factor 1 GATA1 mutations of DS patients 4 years of age at diagnosis
III Determine the relationship of GATA1 mutations with leukemia phenotype and EFS rates of DS patients 4 years of age at diagnosis
IV Determine the relationship of minimal residual disease monitored by flow cytometry and remission status during and after completion of therapy based on bone marrow morphology
V Examine parameters of in vitro drug sensitivity and in vivo Ara-C pharmacokinetics
VI Examine gene expression profiles by microarrays and the relationship to leukemia phenotype and outcome
VII Examine the relationship of functional polymorphisms in phase I and phase II detoxification genes and DNA repair pathways that may modify susceptibility to leukemia and outcome of therapy in DS children
VIII Assess the effect of karyotypic abnormalities on survival IX Establish a DS leukemia cell bank for future biological studies
OUTLINE This is a nonrandomized multicenter study
INDUCTION THERAPY Patients undergo 4 courses of induction therapy Each course is 28 days
COURSE I Patients receive intrathecal IT cytarabine on day 1 and cytarabine IV continuously over 96 hours daunorubicin hydrochloride IV continuously over 96 hours and oral thioguanine twice daily on days 1-4
NOTE Patients with Central Nervous System CNS disease receive cytarabine IT twice weekly for up to 6 doses patients with persistent CNS leukemia after 6 doses of IT cytarabine are removed from the study
COURSE II Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1 2 8 and 9 and asparaginase intramuscularly IM on days 2 and 9
COURSE III Patients receive treatment as in course 1
COURSE IV Patients receive cytarabine IV daunorubicin hydrochloride IV and oral thioguanine as in course 1
Induction therapy continues in the absence of disease progression or unacceptable toxicity Patients with partial response relapsed or refractory disease after completion of course 4 are taken off study Patients achieving complete response proceed to intensification therapy
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
After completion of study treatment patients are followed up periodically for 5 years and then annually thereafter
I Determine the event-free survival EFS and overall survival rates in pediatric patients with Down syndrome DS and acute myeloid leukemia AML or myelodysplastic syndromes MDS treated with induction therapy comprising cytarabine daunorubicin hydrochloride thioguanine and asparaginase followed by intensification therapy comprising cytarabine and etoposide
II Determine if the EFS rate in these patients can be increased with an intensified course of cytarabine therapy during induction therapy compared to the EFS rate of patients in protocol COG-A2971
III Determine if the number of intrathecal chemotherapy treatments can be reduced in these patients
IV Determine if the total cumulative anthracycline dose can be reduced in these patients
SECONDARY OBJECTIVES
I Determine the type and degree of treatment-related toxicity in these patients
II Determine the prevalence of leukemia phenotype and globin transcription factor 1 GATA1 mutations of DS patients 4 years of age at diagnosis
III Determine the relationship of GATA1 mutations with leukemia phenotype and EFS rates of DS patients 4 years of age at diagnosis
IV Determine the relationship of minimal residual disease monitored by flow cytometry and remission status during and after completion of therapy based on bone marrow morphology
V Examine parameters of in vitro drug sensitivity and in vivo Ara-C pharmacokinetics
VI Examine gene expression profiles by microarrays and the relationship to leukemia phenotype and outcome
VII Examine the relationship of functional polymorphisms in phase I and phase II detoxification genes and DNA repair pathways that may modify susceptibility to leukemia and outcome of therapy in DS children
VIII Assess the effect of karyotypic abnormalities on survival IX Establish a DS leukemia cell bank for future biological studies
OUTLINE This is a nonrandomized multicenter study
INDUCTION THERAPY Patients undergo 4 courses of induction therapy Each course is 28 days
COURSE I Patients receive intrathecal IT cytarabine on day 1 and cytarabine IV continuously over 96 hours daunorubicin hydrochloride IV continuously over 96 hours and oral thioguanine twice daily on days 1-4
NOTE Patients with Central Nervous System CNS disease receive cytarabine IT twice weekly for up to 6 doses patients with persistent CNS leukemia after 6 doses of IT cytarabine are removed from the study
COURSE II Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1 2 8 and 9 and asparaginase intramuscularly IM on days 2 and 9
COURSE III Patients receive treatment as in course 1
COURSE IV Patients receive cytarabine IV daunorubicin hydrochloride IV and oral thioguanine as in course 1
Induction therapy continues in the absence of disease progression or unacceptable toxicity Patients with partial response relapsed or refractory disease after completion of course 4 are taken off study Patients achieving complete response proceed to intensification therapy
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
After completion of study treatment patients are followed up periodically for 5 years and then annually thereafter
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10CA098543 | NIH | CTEP | httpsreporternihgovquickSearchU10CA098543 |
| NCI-2009-00318 | REGISTRY | None | None |
| CDR0000492776 | OTHER | None | None |
| COG-AAML0431 | OTHER | None | None |
| AAML0431 | OTHER | None | None |