Trial Outcomes & Findings for WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome (NCT NCT02666950)

Results Overview

Complete response rate will be evaluated over all courses of study treatment. The proportion of CR/CRi responses will be estimated by the number of CR/CRi responses divided by the total number of evaluable patients.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

Up to 17 months

Results posted on

2019-09-06

Participant Flow

Three patients were accrued. Since only one patient was accrued on one arm, patient confidentiality prevents the reporting of results by arm.

Participant milestones

Participant milestones
Measure	Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) Patients receive 20 mg cytarabine (AraC) SC twice daily and 200 mg WEE1 inhibitor (AZD1775) PO daily on days 1-5 and days 8-12 OR receive only 200 mg WEE inhibitor (AZD1775) PO daily on days 1-5, 8-12, 15-19, and 22-26.
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) n=3 Participants Patients receive 20 mg cytarabine (AraC) SC twice daily and 200 mg WEE1 inhibitor (AZD1775) PO daily on days 1-5 and days 8-12 OR receive only 200 mg WEE inhibitor (AZD1775) PO daily on days 1-5, 8-12, 15-19, and 22-26.
Age, Continuous	75.7 years STANDARD_DEVIATION 1.5 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 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	1 Participants n=5 Participants
Race (NIH/OMB) White	2 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
ECOG Performance Status 0	1 Participants n=5 Participants
ECOG Performance Status 2	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 17 months

Population: Since only one patient was accrued on one arm, patient confidentiality prevents the reporting of results by arm.

Complete response rate will be evaluated over all courses of study treatment. The proportion of CR/CRi responses will be estimated by the number of CR/CRi responses divided by the total number of evaluable patients.

Outcome measures

Outcome measures
Measure	Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) n=3 Participants Patients receive 20 mg cytarabine (AraC) SC twice daily and 200 mg WEE1 inhibitor (AZD1775) PO daily on days 1-5 and days 8-12 OR receive only 200 mg WEE inhibitor (AZD1775) PO daily on days 1-5, 8-12, 15-19, and 22-26.
Complete Response Rate (CR or CRi) Per the National Comprehensive Cancer Network (NCCN) Guidelines or According to Specific Criteria From Expert Panels	0 percentage of patients

SECONDARY outcome

Timeframe: Up to 17 months

Population: Since only one patient was accrued on one arm, patient confidentiality prevents the reporting of results by arm.

Clinical benefit as measured by the number of patients who did not receive a RBC transfusion post-Baseline

Outcome measures

Outcome measures
Measure	Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) n=3 Participants Patients receive 20 mg cytarabine (AraC) SC twice daily and 200 mg WEE1 inhibitor (AZD1775) PO daily on days 1-5 and days 8-12 OR receive only 200 mg WEE inhibitor (AZD1775) PO daily on days 1-5, 8-12, 15-19, and 22-26.
Clinical Benefit as Measured by the Number of Patients Who Were Not RBC Transfusion-dependent Post-Baseline	0 Participants

SECONDARY outcome

Timeframe: Up to 17 months

Population: No patients responded, thus no patients were analyzed for this outcome measure. Since only one patient was accrued on one arm, patient confidentiality prevents the reporting of results by arm.

Duration of response defined for all evaluable patients who have achieved a response as the date at which the patient's earliest best objective status is first noted to be a CR/CRi response to the earliest date progression is documented

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 30 days post-treatment

Population: Since only one patient was accrued on one arm, patient confidentiality prevents the reporting of results by arm.

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

Outcome measures

Outcome measures
Measure	Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) n=3 Participants Patients receive 20 mg cytarabine (AraC) SC twice daily and 200 mg WEE1 inhibitor (AZD1775) PO daily on days 1-5 and days 8-12 OR receive only 200 mg WEE inhibitor (AZD1775) PO daily on days 1-5, 8-12, 15-19, and 22-26.
Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment	100 percentage of patients

SECONDARY outcome

Timeframe: From registration to death due to any cause, assessed up to 17 months

Population: Since only one patient was accrued on one arm, patient confidentiality prevents the reporting of results by arm.

Overall survival time is defined as the time from registration to death due to any cause.

Outcome measures

Outcome measures
Measure	Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) n=3 Participants Patients receive 20 mg cytarabine (AraC) SC twice daily and 200 mg WEE1 inhibitor (AZD1775) PO daily on days 1-5 and days 8-12 OR receive only 200 mg WEE inhibitor (AZD1775) PO daily on days 1-5, 8-12, 15-19, and 22-26.
Overall Survival	6 months Interval 4.6 to 7.0

SECONDARY outcome

Timeframe: Up to 17 months

Population: Since only one patient was accrued on one arm, patient confidentiality prevents the reporting of results by arm.

Time to progression (TTP) is defined to be the length of time from study registration to a) date of disease progression as defined by section 11.0 of the protocol, or b) last follow-up. If a patient dies without documentation of disease progression, the patient will be considered to have had a tumor progression at the time of death unless there is sufficient documented evidence to conclude no progression occurred prior to death. Time to progression curves were compared via the log-rank test. Progression is defined as a \>25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions compared to pretreatment MRI and/or CT scan.

Outcome measures

Outcome measures
Measure	Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) n=3 Participants Patients receive 20 mg cytarabine (AraC) SC twice daily and 200 mg WEE1 inhibitor (AZD1775) PO daily on days 1-5 and days 8-12 OR receive only 200 mg WEE inhibitor (AZD1775) PO daily on days 1-5, 8-12, 15-19, and 22-26.
Time to Progression, Defined as the Time From Registration to the Earliest Date of Documentation of Disease Progression	3.9 months Interval 3.8 to 6.9

SECONDARY outcome

Timeframe: Up to 17 months

Population: No patients responded, thus no patients were analyzed for this outcome measure. Since only one patient was accrued on one arm, patient confidentiality prevents the reporting of results by arm.

Time to response, defined as the time from registration to the earliest date of documentation of response. The distribution of time to progression will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 113 days (after course 4)

Continuous biomarker levels will be explored in a graphical manner including mean plots and plots of change and percent change from baseline and other summary measures. Any potential relationships between the baseline level or change in the level of each biomarker and clinical outcome such as overall response, 6-month progression and survival, and adverse event incidence will be further analyzed using Wilcoxon rank sum tests or logistic regression methods, as appropriate. Association between a dichotomized biomarker and overall response will be assessed using a chi-squared test.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 2 years

BFI, as well as linear analog scales capturing early satiety, abdominal discomfort, inactivity, concentration problems, numbness/tingling in the hands/feet, night sweats, itching, bone pain, fever, and weight loss will be used.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 2 years

Scale score trajectories over time and changes from baseline over time will be examined using repeated measures or growth curve models, as appropriate, stream plots and mean plots with standard deviation error bars overall. Scores and changes at each cycle will be statistically tested using paired t-tests, and standardized response means (i.e. effect sizes) (mean of the change from baseline scores at a given cycle, divided by the standard deviation of the change scores) will be interpreted (after applying Middel's adjustment) using Cohen's cut-offs.