Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
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|ClinicalTrials.gov Identifier: NCT02521493|
Recruitment Status : Active, not recruiting
First Posted : August 13, 2015
Last Update Posted : March 30, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Down Syndrome Myelodysplastic Syndrome Myeloid Leukemia Associated With Down Syndrome Myeloproliferative Neoplasm||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 (Clinical Trial)|
|Estimated Enrollment :||312 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome|
|Actual Study Start Date :||November 23, 2015|
|Estimated Primary Completion Date :||June 30, 2024|
|Estimated Study Completion Date :||June 30, 2024|
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.
(This arm is closed to accrual and treatment with amendment #4A 01/07/2019)
Given IT and IV
Drug: Daunorubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Experimental: Arm B (high risk)
INDUCTION II: Patients receive high dose cytarabine IV over 1-3 hours 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 IM or IV over 30 minutes on days 2 and 9. Intensification II continues for a minimum of 28 days.
Given IM or IV
Drug: Asparaginase Erwinia chrysanthemi
Given IM or IV
Given IT and IV
Other: Laboratory Biomarker Analysis
Drug: Mitoxantrone Hydrochloride
- Event-free survival probability at 2 years [ Time Frame: At 2 years ]The Kaplan-Meier method will be used to estimate 2-year event-free survival (EFS) from the end of Induction I along with 95% log-minus-log transformed confidence limits. EFS is defined as the time from the end of Induction I to failure to achieve remission at the end of Induction II, relapse, occurrence of a second malignancy, or death.
- Mean length on protocol therapy [ Time Frame: 6 months ]The mean number of days patients spent on protocol therapy.
- Proportion of patients with an early death [ Time Frame: 1 month ]The proportion of patients experiencing an early death in the first month.
- Overall survival probability at 2 years. [ Time Frame: 2 years ]The Kaplan-Meier method will be used to estimate 2-year Overall Survival (OS) from the end of Induction I along with 95% log-minus-log transformed confidence limits. OS is defined as the time from the end of Induction I to death.
- Proportion with treatment related mortality [ Time Frame: 6 months ]The proportion of patients experiencing a treatment related death will be reported along with a corresponding confidence interval.
- Proportion of patients experiencing a relapse risk [ Time Frame: 2 years ]The proportion of patients experiencing a relapse after achieving remission will be reported along with a corresponding confidence interval.
- Percentage of patients experiencing grade 3 or adverse events [ Time Frame: 6 months ]The percentage of patients experiencing grade 3 or higher toxicity will be reported, where adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
- Mean time to absolute neutrophil count (ANC) recovery [ Time Frame: 6 months ]The mean time to recovery of ANC to at least 1000/uL will be reported.
- Mean duration of hospitalization [ Time Frame: 6 months ]Mean number of days patients are hospitalized.
- Proportion of patients with at least 1 infection [ Time Frame: 6 months ]The proportion of patients having at least one infection will be reported.
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|Ages Eligible for Study:||91 Days to 3 Years (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization [FISH])
Patient has one of the following:
Patient has previously untreated de novo AML and meets the criteria for AML with >= 20% bone marrow blasts as set out in the World Health Organization (WHO) Myeloid Neoplasm classification
- Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive; in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/FISH testing is feasible can be substituted for the marrow exam at diagnosis
- Patient has cytopenias and/or bone marrow blasts but does not meet the criteria for the diagnosis of AML (WHO Myeloid Neoplasm classification) because of < 20% marrow blasts and meets the criteria for a diagnosis of myelodysplastic syndrome (MDS)
For patients who do not meet criteria for AML or MDS as outlined above; patient has a history of transient myeloproliferative disorder (which may or may not have required chemotherapy intervention and:
- Is > 8 weeks since resolution of transient myeloproliferative disease (TMD) with >= 5% blasts, OR
- Has 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
- Patients with promyelocytic leukemia (French-American-British [FAB] M3)
- Patients =< 30 days from the last dose of cytarabine used for treatment of TMD
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): NCT02521493
|Principal Investigator:||Jason N Berman||Children's Oncology Group|
|Responsible Party:||Children's Oncology Group|
|Other Study ID Numbers:||
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 )
|First Posted:||August 13, 2015 Key Record Dates|
|Last Update Posted:||March 30, 2023|
|Last Verified:||March 2023|
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Bone Marrow Diseases
Nervous System Diseases
Genetic Diseases, Inborn