Trial Outcomes & Findings for Pinometostat and Azacitidine in Treating Patients With Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia With 11q23 Rearrangement (NCT NCT03701295)
NCT ID: NCT03701295
Last Updated: 2023-10-18
Results Overview
Safety and tolerability will be assessed by evaluating the number of patients out of 6 who experience a DLT defined as a significant suspected adverse reaction or clinically significant abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications.
COMPLETED
PHASE1/PHASE2
1 participants
Up to day 42
2023-10-18
Participant Flow
Participant milestones
| Measure |
Treatment (Pinometostat, Azacitidine)
Patients receive pinometostat IV continuously on days 1-28 and azacitidine IV over 10-40 minutes or SC for 7 of the first 10 days of the cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Azacitidine: Given IV or SC
Pinometostat: Given IV
|
|---|---|
|
Overall Study
STARTED
|
1
|
|
Overall Study
COMPLETED
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pinometostat and Azacitidine in Treating Patients With Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia With 11q23 Rearrangement
Baseline characteristics by cohort
| Measure |
Treatment (Pinometostat, Azacitidine)
n=1 Participants
Patients receive pinometostat IV continuously on days 1-28 and azacitidine IV over 10-40 minutes or SC for 7 of the first 10 days of the cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Azacitidine: Given IV or SC
Pinometostat: Given IV
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
22 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to day 42Population: Insufficient accrual to analyze this outcome.
Safety and tolerability will be assessed by evaluating the number of patients out of 6 who experience a DLT defined as a significant suspected adverse reaction or clinically significant abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to the time of count recovery after 6 cycles of combination therapyPopulation: Did not open Phase 2.
Will be defined by the 2017 European Leukemia Network guidelines and as the number of patients who achieve a complete response (CR), complete response with incomplete bone marrow recovery (CRi), partial response (PR), or morphologic leukemia-free state (MLFS), with or without minimal residual disease (MRD), at any time point.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to day 42Population: Insufficient accrual to analyze this outcome.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to day 28Population: Insufficient accrual to analyze this outcome.
Will compare quantitative methylation and methylation valence (e.g. if H3K27 has been methylated once, twice, or three times) from baseline and subsequent bone marrow samples using descriptive statistics and graphical displays. A Wilcoxon signed rank test will be used to assess post-treatment differences as compared to baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to day 28Population: Insufficient accrual to analyze this outcome.
Will compare expression level by quantitative polymerase chain reaction (qPCR) of HOXA9 and Meis1 levels from baseline and subsequent bone marrow samples using descriptive statistics and graphical displays. A Wilcoxon signed rank test will be used to assess post-treatment differences as compared to baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to day 28Population: Insufficient accrual to analyze this outcome.
Samples will be banked, and cytogenetic and fluorescence in situ hybridization (FISH) analysis of these cells will be performed to evaluate for the presence of MLL-rearrangement in patients who respond to therapy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to day 28Population: Insufficient accrual to analyze this outcome.
Will evaluate differentiation by performing a differential on the bone marrow biopsy and peripheral blood samples at baseline and from subsequent time points and assessing percentage of monocytes / neutrophils, bands, and myeloid forms present.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 1 month post-treatmentPopulation: Did not open Phase 2.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 1 month post-treatmentPopulation: Did not open Phase 2.
Patients will be stratified based on treatment for relapsed / refractory or previously untreated disease. The response of each stratum to combination therapy, defined as CR, CRi, MLFS, or PR, with or without MRD, on bone marrow biopsy as defined by the 2017 European Leukemia Network guidelines, will be described. Kaplan-Meier estimates will be calculated and compared for each stratum. A report will be generated to look at all patients, all eligible patients who were enrolled, and all evaluable patients.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to 1 month post-treatmentPopulation: Did not open Phase 2.
Will compare quantitative methylation and methylation valence (e.g. if H3K27 has been methylated once, twice, or three times) from baseline and subsequent bone marrow samples using descriptive statistics and graphical displays. A Wilcoxon signed rank test will be used to assess post-treatment differences as compared to baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to 1 month post-treatmentPopulation: Did not open Phase 2.
Will compare expression level by qPCR of HOXA9 and Meis1 levels from baseline and subsequent bone marrow samples using descriptive statistics and graphical displays. A Wilcoxon signed rank test will be used to assess post-treatment differences as compared to baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 1 month post-treatmentPopulation: Did not open Phase 2.
Samples will be banked, and cytogenetic and FISH analysis of these cells will be performed to evaluate for the presence of MLL-rearrangement in patients who respond to therapy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to the end of course 1Population: Did not open Phase 2.
Will evaluate differentiation by performing a differential on the bone marrow biopsy and peripheral blood samples at baseline and from subsequent time points and assessing percentage of monocytes / neutrophils, bands, and myeloid forms present.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 1 month post-treatmentPopulation: Insufficient accrual to analyze this outcome.
Will correlate with systemic azacitidine exposure and pharmacodynamics effects.
Outcome measures
Outcome data not reported
Adverse Events
Treatment (Pinometostat, Azacitidine)
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
ETCTN Grants Administrative Manager
Johns Hopkins University
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60