Ignite Creation Date:
2024-06-16 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06429449
Status:
RECRUITING
Last Update Posted:
2024-05-28
First Post:
2024-05-13
Brief Title:
Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia
Sponsor:
University of Colorado Denver
Organization:
University of Colorado Denver
Study Overview
Official Title:
Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia
Status:
RECRUITING
Status Verified Date:
2024-08
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 is an open label phase 1 study for AML subjects with relapsed or refractory disease or subjects in morphologic remission with MRD after first line therapy with venetoclaxHMA A preliminary dose-finding cohort will be followed by 3 expansion cohorts
Detailed Description:
This is an open label phase 1 study for AML subjects with relapsed or refractory disease or subjects in morphologic remission with MRD after first line therapy with venetoclaxHMA A preliminary dose-finding cohort will be followed by 3 expansion cohorts
Cohort 1 will be a conventional 33 dose-escalation study to determine maximum tolerated MTD or recommended dose of mitoxantrone when used with venetoclaxazacitidine Subjects who are refractory to first-line therapy with venetoclaxHMA or who respond and then relapse after first line therapy with venetoclaxHMA will enroll in the study and receive a subsequent cycle of venetoclaxazacitidine at the dose and schedule being administered per the standard of care along with a starting dose of 4mgm2 of mitoxantrone administered IV on days 1-4 Depending on the absence or frequency of dose-limiting toxicities additional patients will be enrolled at the appropriate dose levels increasing by 2mgm2 per cycle per the 33 design until the MTD or a dose of 10mgm2 of mitoxantrone is reached The dose escalation phase will conclude when the MTD is determined if the MTD is not reached a recommendation for a dose of mitoxantrone in combination with venetoclaxazacitidine will be made based on toxicity and efficacy data
After the establishment of the MTD or recommended dose of mitoxantrone an expansion cohort cohort 2 will open 10 subjects who are refractory to first-line therapy with venetoclaxHMA or who respond and then relapse after first line therapy with venetoclaxHMA will enroll in the study and receive a subsequent cycle of venetoclaxazacitidine at the dose and schedule being administered per the standard of care with the determined MTDrecommended dose of IV mitoxantrone given on days 1-4 On day 28 - 7 days of this cycle a bone marrow biopsy will be repeated In the absence of a 50 blast reduction from baseline the subject will discontinue the study If a CR CRi MLFS or blast reduction from baseline of 50 occurs the subject can continue sequential cycles of venetoclaxazacitidine at the dose and schedule being administered per the standard of care with the MTDrecommended dose of mitoxantrone on days 1-4 for up to 3 total cycles No subject will receive 3 cycles of mitoxantrone After mitoxantrone cycles have been completed subjects will receive a bone marrow biopsy after the third cycle and then continue bone marrow biopsies with MRD assessments every 6 months until disease progression or the administration of any therapy other than venetoclaxazacitidine at which time the subject will be discontinued from the study
In cohort 3 subjects who are in a morphologic remission with MRD after 3 cycles of standard of care venetoclaxHMA will enroll and receive mitoxantrone on days 1-4 at a dose to-be-determined that is below the MTD from cohort 1 concurrently with venetoclaxazacitidine at the dose and schedule being administered per the standard of care over a 28-day treatment cycle A bone marrow biopsy with MRD assessment will be performed on day 28 - 7 days If MRD conversion to negative occurs subsequent treatment cycles will continue to administer venetoclaxazacitidine at the dose and schedule being administered per the standard of care with the to-be-determined dose of mitoxantrone on days 1-4 for a maximum of three total cycles of mitoxantrone If MRD conversion to negative does not occur the next cycle may escalate the mitoxantrone dose to a level to-be-determined and not exceeding the MTD with venetoclaxazacitidine at the dose and schedule being administered per the standard of care If MRD conversion to negative occurs subsequent treatment cycles will continue to administer venetoclaxazacitidine at the dose and schedule being administered per the standard of care with the to-be-determined dose of IV mitoxantrone on days 1-4 for a maximum of three total cycles of mitoxantrone If MRD conversion to negative does not occur the next cycle may escalate the mitoxantrone to a level to-be-determined and not exceeding the MTD with venetoclaxazacitidine at the dose and schedule being administered per the standard of care Subjects will not receive 3 cycles of mitoxantrone After mitoxantrone cycles have been completed subjects will continue bone marrow biopsies with MRD assessments every 6 months until disease progression or the administration of any therapy other than venetoclaxazacitidine at which time the subject will be discontinued from the study
In cohort 4 subjects who are in a morphologic remission with MRD after 3 cycles of standard of care venetoclaxHMA will enroll 28-50 days after the start of the previous venetoclaxHMA cycle They will receive mitoxantrone IV on days 1-4 at a dose to-be-determined that is below the MTD from cohort 1 on day 14 the subject will start venetoclaxazacitidine at the dose and schedule being administered per the standard of care On day 42 - 7 days a bone marrow biopsy with MRD assessment will be repeated If MRD conversion to negative occurs subsequent treatment cycles will continue to administer venetoclaxazacitidine at the dose and schedule being administered per the standard of care with the to-be-determined dose of IV mitoxantrone on days 1-4 for a maximum of three total cycles of mitoxantrone If MRD conversion to negative does not occur the next cycle will retain the same schedule and may escalate the mitoxantrone to a dose level to-be-determined and not exceeding the MTD If MRD conversion to negative occurs one additional cycle of mitoxantrone at this dose with venetoclaxazacitidine at the dose and schedule being administered per the standard of care will be given If MRD conversion to negative does not occur the next cycle will retain the same schedule and may escalate the mitoxantrone to a level to-be-determined and not exceeding the MTD No subject will receive 3 cycles of mitoxantrone After mitoxantrone cycles have been completed subjects will continue bone marrow biopsies with MRD assessments every 6 months until disease progression or the administration of any therapy other than venetoclaxazacitidine at which time the subject will be discontinued from the study
Cohort 1 will be a conventional 33 dose-escalation study to determine maximum tolerated MTD or recommended dose of mitoxantrone when used with venetoclaxazacitidine Subjects who are refractory to first-line therapy with venetoclaxHMA or who respond and then relapse after first line therapy with venetoclaxHMA will enroll in the study and receive a subsequent cycle of venetoclaxazacitidine at the dose and schedule being administered per the standard of care along with a starting dose of 4mgm2 of mitoxantrone administered IV on days 1-4 Depending on the absence or frequency of dose-limiting toxicities additional patients will be enrolled at the appropriate dose levels increasing by 2mgm2 per cycle per the 33 design until the MTD or a dose of 10mgm2 of mitoxantrone is reached The dose escalation phase will conclude when the MTD is determined if the MTD is not reached a recommendation for a dose of mitoxantrone in combination with venetoclaxazacitidine will be made based on toxicity and efficacy data
After the establishment of the MTD or recommended dose of mitoxantrone an expansion cohort cohort 2 will open 10 subjects who are refractory to first-line therapy with venetoclaxHMA or who respond and then relapse after first line therapy with venetoclaxHMA will enroll in the study and receive a subsequent cycle of venetoclaxazacitidine at the dose and schedule being administered per the standard of care with the determined MTDrecommended dose of IV mitoxantrone given on days 1-4 On day 28 - 7 days of this cycle a bone marrow biopsy will be repeated In the absence of a 50 blast reduction from baseline the subject will discontinue the study If a CR CRi MLFS or blast reduction from baseline of 50 occurs the subject can continue sequential cycles of venetoclaxazacitidine at the dose and schedule being administered per the standard of care with the MTDrecommended dose of mitoxantrone on days 1-4 for up to 3 total cycles No subject will receive 3 cycles of mitoxantrone After mitoxantrone cycles have been completed subjects will receive a bone marrow biopsy after the third cycle and then continue bone marrow biopsies with MRD assessments every 6 months until disease progression or the administration of any therapy other than venetoclaxazacitidine at which time the subject will be discontinued from the study
In cohort 3 subjects who are in a morphologic remission with MRD after 3 cycles of standard of care venetoclaxHMA will enroll and receive mitoxantrone on days 1-4 at a dose to-be-determined that is below the MTD from cohort 1 concurrently with venetoclaxazacitidine at the dose and schedule being administered per the standard of care over a 28-day treatment cycle A bone marrow biopsy with MRD assessment will be performed on day 28 - 7 days If MRD conversion to negative occurs subsequent treatment cycles will continue to administer venetoclaxazacitidine at the dose and schedule being administered per the standard of care with the to-be-determined dose of mitoxantrone on days 1-4 for a maximum of three total cycles of mitoxantrone If MRD conversion to negative does not occur the next cycle may escalate the mitoxantrone dose to a level to-be-determined and not exceeding the MTD with venetoclaxazacitidine at the dose and schedule being administered per the standard of care If MRD conversion to negative occurs subsequent treatment cycles will continue to administer venetoclaxazacitidine at the dose and schedule being administered per the standard of care with the to-be-determined dose of IV mitoxantrone on days 1-4 for a maximum of three total cycles of mitoxantrone If MRD conversion to negative does not occur the next cycle may escalate the mitoxantrone to a level to-be-determined and not exceeding the MTD with venetoclaxazacitidine at the dose and schedule being administered per the standard of care Subjects will not receive 3 cycles of mitoxantrone After mitoxantrone cycles have been completed subjects will continue bone marrow biopsies with MRD assessments every 6 months until disease progression or the administration of any therapy other than venetoclaxazacitidine at which time the subject will be discontinued from the study
In cohort 4 subjects who are in a morphologic remission with MRD after 3 cycles of standard of care venetoclaxHMA will enroll 28-50 days after the start of the previous venetoclaxHMA cycle They will receive mitoxantrone IV on days 1-4 at a dose to-be-determined that is below the MTD from cohort 1 on day 14 the subject will start venetoclaxazacitidine at the dose and schedule being administered per the standard of care On day 42 - 7 days a bone marrow biopsy with MRD assessment will be repeated If MRD conversion to negative occurs subsequent treatment cycles will continue to administer venetoclaxazacitidine at the dose and schedule being administered per the standard of care with the to-be-determined dose of IV mitoxantrone on days 1-4 for a maximum of three total cycles of mitoxantrone If MRD conversion to negative does not occur the next cycle will retain the same schedule and may escalate the mitoxantrone to a dose level to-be-determined and not exceeding the MTD If MRD conversion to negative occurs one additional cycle of mitoxantrone at this dose with venetoclaxazacitidine at the dose and schedule being administered per the standard of care will be given If MRD conversion to negative does not occur the next cycle will retain the same schedule and may escalate the mitoxantrone to a level to-be-determined and not exceeding the MTD No subject will receive 3 cycles of mitoxantrone After mitoxantrone cycles have been completed subjects will continue bone marrow biopsies with MRD assessments every 6 months until disease progression or the administration of any therapy other than venetoclaxazacitidine at which time the subject will be discontinued from the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None