Trial Outcomes & Findings for Low Dose Daunorubicin in Pediatric Relapsed/Refractory Acute Leukemia (NCT NCT04562792)
NCT ID: NCT04562792
Last Updated: 2023-06-28
Results Overview
Feasibility failure due to progressive leukemia is defined as a rise in absolute blast count (ABC) of \>10,000/day on two consecutive days that continues to increase \>10,000/day after starting hydroxyurea.
COMPLETED
PHASE2
1 participants
24 months
2023-06-28
Participant Flow
Participant milestones
| Measure |
Patients With Relapsed/Refractory ALL and AML
Patients in this arm will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
Daunorubicin: Eligible patients with relapsed and/or refractory acute leukemia will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
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|---|---|
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Overall Study
STARTED
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1
|
|
Overall Study
COMPLETED
|
1
|
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Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Low Dose Daunorubicin in Pediatric Relapsed/Refractory Acute Leukemia
Baseline characteristics by cohort
| Measure |
Patients With Relapsed/Refractory ALL and AML
n=1 Participants
Patients in this arm will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
Daunorubicin: Eligible patients with relapsed and/or refractory acute leukemia will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
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|---|---|
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Age, Categorical
<=18 years
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1 Participants
n=99 Participants
|
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Age, Categorical
Between 18 and 65 years
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0 Participants
n=99 Participants
|
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Age, Categorical
>=65 years
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0 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
African American
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1 Participants
n=99 Participants
|
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Region of Enrollment
United States
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1 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: Data collected but analysis not performed due to small number of participants and inability to run analysis without more samples
Feasibility failure due to progressive leukemia is defined as a rise in absolute blast count (ABC) of \>10,000/day on two consecutive days that continues to increase \>10,000/day after starting hydroxyurea.
Outcome measures
| Measure |
Patients With Relapsed/Refractory ALL and AML
n=1 Participants
Patients in this arm will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
Daunorubicin: Eligible patients with relapsed and/or refractory acute leukemia will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
|
|---|---|
|
Incidence of Low Dose Daunorubicin Feasbility as Assessed by Absolute Blast Count
Patients with a rise in absolute blast count (ABC) of >10,000/day on two consecutive days
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0 Participants
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Incidence of Low Dose Daunorubicin Feasbility as Assessed by Absolute Blast Count
Patients without a rise in absolute blast count (ABC) of >10,000/day on two consecutive days
|
1 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: Data collected but analysis not performed due to small number of participants and inability to run analysis without more samples
Low dose daunorubicin will also be deemed not feasible if there is evidence of progression of extramedullary leukemia such progression of chloroma or leukemia cutis. or if the patient experiences uncontrollable nausea and/or vomiting.
Outcome measures
| Measure |
Patients With Relapsed/Refractory ALL and AML
n=1 Participants
Patients in this arm will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
Daunorubicin: Eligible patients with relapsed and/or refractory acute leukemia will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
|
|---|---|
|
Incidence of Low Dose Daunorubicin Feasbility as Assessed by Extramedullary Leukemia Progression
Patients with evidence of progression of extramedullary leukemia
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0 Participants
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Incidence of Low Dose Daunorubicin Feasbility as Assessed by Extramedullary Leukemia Progression
Patients without evidence of progression of extramedullary leukemia
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1 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: Data collected but analysis not performed due to small number of participants and inability to run analysis without more samples
Low dose daunorubicin will also be deemed not feasible if the patient experiences uncontrollable nausea and/or vomiting.
Outcome measures
| Measure |
Patients With Relapsed/Refractory ALL and AML
n=1 Participants
Patients in this arm will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
Daunorubicin: Eligible patients with relapsed and/or refractory acute leukemia will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
|
|---|---|
|
Incidence of Low Dose Daunorubicin Feasbility as Assessed by Patient Symptoms
Uncontrollable Nausea or Vomiting
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0 Participants
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Incidence of Low Dose Daunorubicin Feasbility as Assessed by Patient Symptoms
Patients with no uncontrollable nausea or vomiting
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1 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: This particular outcome measure requires analysis to be run in the laboratory. This was not performed and therefore there is not data to report.
Leukemia stem cells (LSCs) are known to be resistant to chemotherapy which may lead to treatment failure. In vitro studies have shown that targeted anthracycline treatment reduces immune checkpoint expression on LSCs, potentially sensitizing LSCs to cytotoxic T-cells. This will be measured in our study.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 24 monthsPopulation: This particular outcome measure requires analysis to be run in the laboratory. This was not performed and therefore there is not data to report.
Chemotherapy is typically administered at maximum tolerated doses which leads to secondary immunosuppression. In other words, beneficial immunologic side effects can be weakened if chemotherapy is given at high doses. The Wnt pathway (which plays a key role in chemoresistance of LSCs) reduces T cell recruitment to tumors. Available data in murine models indicates that targeted anthracycline treatment expands cancer-targeting T-cells while inhibiting populations known to help cancer cells evade the immune system. This will be measured in our study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 monthsPopulation: One patient analyzed.
Serial daunorubicin levels for evaluation of maximum concentration will be drawn prior to infusion and at 5, 20 and 40 minutes and at hours 1,2,4,8 and 24 post infusion.
Outcome measures
| Measure |
Patients With Relapsed/Refractory ALL and AML
n=1 Participants
Patients in this arm will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
Daunorubicin: Eligible patients with relapsed and/or refractory acute leukemia will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
|
|---|---|
|
Pharmacokinetic Parameters of Low Dose Daunorubicin in Children With Relapsed/Refractory AML and ALL as Assessed by Maximum Concentration.
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18.7 ng/mL
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SECONDARY outcome
Timeframe: 24 monthsPopulation: One patient analyzed.
Serial daunorubicin levels for evaluation of time at maximum concentration will be drawn prior to infusion and at 5, 20 and 40 minutes and hours 1,2,4,8 and 24 post infusion.
Outcome measures
| Measure |
Patients With Relapsed/Refractory ALL and AML
n=1 Participants
Patients in this arm will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
Daunorubicin: Eligible patients with relapsed and/or refractory acute leukemia will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
|
|---|---|
|
Pharmacokinetic Parameters of Low Dose Daunorubicin in Children With Relapsed/Refractory AML and ALL as Assessed by Time at Maximum Concentration.
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0.33333 hour
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SECONDARY outcome
Timeframe: 24 monthsPopulation: One patient analyzed.
Serial daunorubicin levels for evaluation of exposure by measuring area under the curve will be drawn prior to infusion and at 5, 20 and 40 minutes and hours 1,2,4,8 and 24 post infusion.
Outcome measures
| Measure |
Patients With Relapsed/Refractory ALL and AML
n=1 Participants
Patients in this arm will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
Daunorubicin: Eligible patients with relapsed and/or refractory acute leukemia will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
|
|---|---|
|
Pharmacokinetic Parameters of Low Dose Daunorubicin in Children With Relapsed/Refractory AML and ALL as Assessed by Area Under the Curve.
|
20.889865 hr*ng/mL
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SECONDARY outcome
Timeframe: 24 monthsPopulation: One patient analyzed.
Serial daunorubicin levels for evaluation of exposure by measuring elimination half-life will be drawn prior to infusion and at 5, 20 and 40 minutes and hours 1,2,4,8 and 24 post infusion.
Outcome measures
| Measure |
Patients With Relapsed/Refractory ALL and AML
n=1 Participants
Patients in this arm will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
Daunorubicin: Eligible patients with relapsed and/or refractory acute leukemia will receive daunorubicin 6.75mg/m2 daily for 5 consecutive days.
|
|---|---|
|
Pharmacokinetic Parameters of Low Dose Daunorubicin in Children With Relapsed/Refractory AML and ALL as Assessed by Elimination Half-life
|
1.8588 hour
|
Adverse Events
Patients With Relapsed/Refractory ALL and AML
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place