Trial Outcomes & Findings for Using the Anticancer Drug Olaparib to Treat Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome With an Isocitrate Dehydrogenase (IDH) Mutation (NCT NCT03953898)

NCT ID: NCT03953898

Last Updated: 2025-09-10

Results Overview

Will be evaluated by Myelodysplastic Syndrome International Working Group (IWG) 2006 criteria (Cheson et al., 2006) and acute myeloid leukemia (AML) IWG 2003 criteria (Cheson et al., 2003) after 6 cycles of treatment. Cumulative ORR will include complete remission (CR), complete remission with incomplete blood count recovery (CRi), partial response (PR), and bone marrow complete remission (marrow CR) achieved at least at one point during these 6 cycles.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Up to 6 cycles

Results posted on

2025-09-10

Participant Flow

Participant milestones

Participant milestones
Measure
Treatment (Olaparib)
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity, or absence of remission after 6 cycles for patients without prior exposure to IDH inhibitors, or for up to 12 cycles. Patients also undergo bone marrow aspiration and collection of blood throughout the study. Biospecimen Collection: Undergo collection of blood Bone Marrow Aspiration: Undergo bone marrow aspiration Olaparib: Given PO
Overall Study
STARTED
14
Overall Study
Started Therapy
12
Overall Study
COMPLETED
0
Overall Study
NOT COMPLETED
14

Reasons for withdrawal

Reasons for withdrawal
Measure
Treatment (Olaparib)
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity, or absence of remission after 6 cycles for patients without prior exposure to IDH inhibitors, or for up to 12 cycles. Patients also undergo bone marrow aspiration and collection of blood throughout the study. Biospecimen Collection: Undergo collection of blood Bone Marrow Aspiration: Undergo bone marrow aspiration Olaparib: Given PO
Overall Study
Lack of Efficacy
8
Overall Study
Death
3
Overall Study
Withdrawal by Subject
2
Overall Study
Adverse Event
1

Baseline Characteristics

Using the Anticancer Drug Olaparib to Treat Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome With an Isocitrate Dehydrogenase (IDH) Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment (Olaparib)
n=14 Participants
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity, or absence of remission after 6 cycles for patients without prior exposure to IDH inhibitors, or for up to 12 cycles. Patients also undergo bone marrow aspiration and collection of blood throughout the study. Biospecimen Collection: Undergo collection of blood Bone Marrow Aspiration: Undergo bone marrow aspiration Olaparib: Given PO
Age, Continuous
76 years
n=5 Participants
Sex: Female, Male
Female
7 Participants
n=5 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
Race/Ethnicity, Customized
Race/Ethnicity · White
10 Participants
n=5 Participants
Race/Ethnicity, Customized
Race/Ethnicity · Latino
2 Participants
n=5 Participants
Race/Ethnicity, Customized
Race/Ethnicity · Asian
1 Participants
n=5 Participants
Race/Ethnicity, Customized
Race/Ethnicity · Black/African American
0 Participants
n=5 Participants
Race/Ethnicity, Customized
Race/Ethnicity · Missing
1 Participants
n=5 Participants
Region of Enrollment
United States
14 participants
n=5 Participants
ECOG PS
0: Fully active
3 Participants
n=5 Participants
ECOG PS
1: Unable to do strenuous activities
9 Participants
n=5 Participants
ECOG PS
2: Able to walk and manage self-care
2 Participants
n=5 Participants
ECOG PS
3: Confined to bed or a chair more than 50% of waking hours
0 Participants
n=5 Participants
ECOG PS
4: Completely disabled
0 Participants
n=5 Participants
ECOG PS
5: Death
0 Participants
n=5 Participants
IDH mutation
IDH1
3 Participants
n=5 Participants
IDH mutation
IDH2
9 Participants
n=5 Participants
IDH mutation
IDH1 and IDH2
1 Participants
n=5 Participants
IDH mutation
MISSING
1 Participants
n=5 Participants
Prior IDH inhibitor exposure
Yes
8 Participants
n=5 Participants
Prior IDH inhibitor exposure
No
6 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 cycles

Population: Participants receiving treatment

Will be evaluated by Myelodysplastic Syndrome International Working Group (IWG) 2006 criteria (Cheson et al., 2006) and acute myeloid leukemia (AML) IWG 2003 criteria (Cheson et al., 2003) after 6 cycles of treatment. Cumulative ORR will include complete remission (CR), complete remission with incomplete blood count recovery (CRi), partial response (PR), and bone marrow complete remission (marrow CR) achieved at least at one point during these 6 cycles.

Outcome measures

Outcome measures
Measure
Treatment (Olaparib)
n=12 Participants
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity, or absence of remission after 6 cycles for patients without prior exposure to IDH inhibitors, or for up to 12 cycles. Patients also undergo bone marrow aspiration and collection of blood throughout the study. Biospecimen Collection: Undergo collection of blood Bone Marrow Aspiration: Undergo bone marrow aspiration Olaparib: Given PO
Cumulative Overall Response Rate (ORR)
Complete remission (CR)
0 Participants
Cumulative Overall Response Rate (ORR)
Complete remission with incomplete hematologic response
0 Participants
Cumulative Overall Response Rate (ORR)
Complete remission with partial hematologic response
0 Participants
Cumulative Overall Response Rate (ORR)
Composite CR rate (CR+CRi+CRh)
0 Participants
Cumulative Overall Response Rate (ORR)
No Response
12 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: Participants receiving treatment

The effectiveness of the drug in patients for each cohort will be independently assessed by ORR. The exact two-sided 95% confidence intervals (CI) for the ORR will be reported. The CI based on the Greenwoods variance will be reported.

Outcome measures

Outcome measures
Measure
Treatment (Olaparib)
n=12 Participants
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity, or absence of remission after 6 cycles for patients without prior exposure to IDH inhibitors, or for up to 12 cycles. Patients also undergo bone marrow aspiration and collection of blood throughout the study. Biospecimen Collection: Undergo collection of blood Bone Marrow Aspiration: Undergo bone marrow aspiration Olaparib: Given PO
ORR
OR = Yes
0 Participants
ORR
OR = No
12 Participants

SECONDARY outcome

Timeframe: From first day of therapy to the time of documentation of progression, death of any cause, or last follow-up, whichever comes first, assessed up to 12 months

Population: Participants receiving treatment

Will be estimated using the Kaplan-Meier method with the 95% CIs. The CI based on the Greenwoods variance will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the odds ratios and the adjusted 95% confidence interval will be reported.

Outcome measures

Outcome measures
Measure
Treatment (Olaparib)
n=12 Participants
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity, or absence of remission after 6 cycles for patients without prior exposure to IDH inhibitors, or for up to 12 cycles. Patients also undergo bone marrow aspiration and collection of blood throughout the study. Biospecimen Collection: Undergo collection of blood Bone Marrow Aspiration: Undergo bone marrow aspiration Olaparib: Given PO
Progression-free Survival (PFS)
2.3 months
Interval 0.4 to 5.6

SECONDARY outcome

Timeframe: From first day of therapy to the time of death or last follow-up, whichever comes first, assessed up to 12 months

Population: Participants receiving treatment

Will be estimated using the Kaplan-Meier method with the 95% CIs. The CI based on the Greenwoods variance will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the odds ratios and the adjusted 95% confidence interval will be reported.

Outcome measures

Outcome measures
Measure
Treatment (Olaparib)
n=12 Participants
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity, or absence of remission after 6 cycles for patients without prior exposure to IDH inhibitors, or for up to 12 cycles. Patients also undergo bone marrow aspiration and collection of blood throughout the study. Biospecimen Collection: Undergo collection of blood Bone Marrow Aspiration: Undergo bone marrow aspiration Olaparib: Given PO
Overall Survival (OS)
3.4 months
Interval 0.4 to 35.3

SECONDARY outcome

Timeframe: From first documentation of response to the time of documentation of progression, death of any cause, or last follow-up, whichever comes first, assessed up to 12 months

Population: no patients responded to treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

Population: 12 pariticipants received treatment.

Non-hematologic toxicity will be evaluated by Common Terminology Criteria for Adverse Events version 5 criteria. Presented are the count of those that experienced at least one non-serious adverse event.

Outcome measures

Outcome measures
Measure
Treatment (Olaparib)
n=12 Participants
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity, or absence of remission after 6 cycles for patients without prior exposure to IDH inhibitors, or for up to 12 cycles. Patients also undergo bone marrow aspiration and collection of blood throughout the study. Biospecimen Collection: Undergo collection of blood Bone Marrow Aspiration: Undergo bone marrow aspiration Olaparib: Given PO
Incidence of Adverse Events
12 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 months

The Mann-Whitney U test will be used to test for differences in post-treatment plasma 2HG concentrations between patients with a response to treatment and those without. Will also test for differences in Delta2HG (defined as pre-treatment minus post-treatment plasma concentration) between patients with a response to treatment and those without. Differences with p =\< 0.05 will be considered significant. The area under the receiver operating characteristic curve (ROC AUC) will be calculated to determine the cutoff value of the Delta2HG difference. The optimal cutoff value will be determined at the point on the ROC curve at (sensitivity + specificity - 1) is maximized.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 months

Will define MRD based on the variation of the variant allele frequency of the IDH1/2 mutation in the bone marrow of the patients before and during therapy. Will evaluate two different variables: MRD negativity (defined by the absence of detection of the IDH mutant in the sample) and the molecular response (defined by the log reduction of the frequency of the mutant allele). MRD negativity is a qualitative variable and will be reported as a percentage with 95% confidence interval for each time point and mutation. Will compare the different groups using a Chi-Square test. Molecular response is a quantitative variable reported as a median, min and max for each time point and we will use a student t test for the comparison of the different groups.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 months

Will be estimated using Poisson distribution model as the fraction of positive reads divided by total reads containing a target. The limit of detection will be defined for each mutation as the mean value of IDH1/2 wild-type controls plus three standard deviations.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Olaparib)

Serious events: 9 serious events
Other events: 12 other events
Deaths: 10 deaths

Serious adverse events

Serious adverse events
Measure
Treatment (Olaparib)
n=12 participants at risk
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity, or absence of remission after 6 cycles for patients without prior exposure to IDH inhibitors, or for up to 12 cycles. Patients also undergo bone marrow aspiration and collection of blood throughout the study. Biospecimen Collection: Undergo collection of blood Bone Marrow Aspiration: Undergo bone marrow aspiration Olaparib: Given PO
Gastrointestinal disorders
Constipation
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
General disorders
Death NOS
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
Dyspnea
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Blood and lymphatic system disorders
Febrile neutropenia
25.0%
3/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Fungemia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
Hypoxia
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Infections and infestations - Other, specify
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Blood and lymphatic system disorders
Leukocytosis
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Lung infection
33.3%
4/12 • Median time from 1st dose to off-study: 74.5 days
Gastrointestinal disorders
Mucositis oral
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Cardiac disorders
Myocardial infarction
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
Respiratory failure
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Sepsis
33.3%
4/12 • Median time from 1st dose to off-study: 74.5 days
Cardiac disorders
Sinus tachycardia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Skin and subcutaneous tissue disorders
Skin infection
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days

Other adverse events

Other adverse events
Measure
Treatment (Olaparib)
n=12 participants at risk
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity, or absence of remission after 6 cycles for patients without prior exposure to IDH inhibitors, or for up to 12 cycles. Patients also undergo bone marrow aspiration and collection of blood throughout the study. Biospecimen Collection: Undergo collection of blood Bone Marrow Aspiration: Undergo bone marrow aspiration Olaparib: Given PO
Blood and lymphatic system disorders
Anemia
50.0%
6/12 • Median time from 1st dose to off-study: 74.5 days
Blood and lymphatic system disorders
Febrile neutropenia
33.3%
4/12 • Median time from 1st dose to off-study: 74.5 days
Blood and lymphatic system disorders
Leukocytosis
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Cardiac disorders
Atrial fibrillation
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Cardiac disorders
Myocardial infarction
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Cardiac disorders
Sinus tachycardia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Eye disorders
Vision decreased
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
General disorders
Disease progression
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
General disorders
Fatigue
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
General disorders
Fever
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
General disorders
Flu like symptoms
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
General disorders
Neck edema
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Gastrointestinal disorders
Diarrhea
25.0%
3/12 • Median time from 1st dose to off-study: 74.5 days
Gastrointestinal disorders
Constipation
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Gastrointestinal disorders
Gastroesophageal reflux disease
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Gastrointestinal disorders
Nausea
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Gastrointestinal disorders
Vomiting
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Gastrointestinal disorders
Abdominal pain
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Gastrointestinal disorders
Mucositis oral
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Gastrointestinal disorders
Oral hemorrhage
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Infections & infestations - Other - Sepsis
25.0%
3/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Lung infection
25.0%
3/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Skin infection
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Urinary tract infection
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Cytomegalovirus infection reactivation
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Fungemia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Infections & infestations - Other - Covid-19
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Lip infection
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Infections and infestations
Upper respiratory infection
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Injury, poisoning and procedural complications
Bruising
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Injury, poisoning and procedural complications
Infusion related reaction
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
Platelet count decreased
41.7%
5/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
Neutrophil count decreased
25.0%
3/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
White blood cell decreased
25.0%
3/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
ALT increased
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
AST increased
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
Activated PTT prolonged
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
Alkaline phosphatase increased
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
Investigations - Other, specify - Night Sweat
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Investigations
Lymphocyte count decreased
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Metabolism and nutrition disorders
Hyperglycemia
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Metabolism and nutrition disorders
Hypocalcemia
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Metabolism and nutrition disorders
Hypomagnesemia
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Metabolism and nutrition disorders
Hypophosphatemia
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Metabolism and nutrition disorders
Anorexia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Metabolism and nutrition disorders
Hyperphosphatemia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Metabolism and nutrition disorders
Hypoalbuminemia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Metabolism and nutrition disorders
Hypokalemia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Metabolism and nutrition disorders
Hyponatremia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Musculoskeletal and connective tissue disorders
Back pain
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Musculoskeletal and connective tissue disorders
Muscle cramp
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Musculoskeletal and connective tissue disorders
Myalgia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Musculoskeletal and connective tissue disorders
Neck pain
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms - Other - Adrenal Cyst
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms - Other - Lung Nodule
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Nervous system disorders
Dizziness
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Nervous system disorders
Dysgeusia
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Nervous system disorders
Headache
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Psychiatric disorders
Hallucinations
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Renal and urinary disorders
Chronic kidney disease
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Renal and urinary disorders
Urinary frequency
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Renal and urinary disorders
Urinary retention
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Reproductive system and breast disorders
Vaginal hemorrhage
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Respiratory, thoracic and mediastinal disorders
Dyspnea
33.3%
4/12 • Median time from 1st dose to off-study: 74.5 days
Respiratory, thoracic and mediastinal disorders
Hypoxia
25.0%
3/12 • Median time from 1st dose to off-study: 74.5 days
Respiratory, thoracic and mediastinal disorders
Sore throat
16.7%
2/12 • Median time from 1st dose to off-study: 74.5 days
Respiratory, thoracic and mediastinal disorders
Cough
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Respiratory, thoracic and mediastinal disorders
Epistaxis
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Respiratory, thoracic and mediastinal disorders
Respiratory failure
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Skin and subcutaneous tissue disorders
Skin & subcutaneous tissue -Other - Cellulitis
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Vascular disorders
Hematoma
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days
Vascular disorders
Hypotension
8.3%
1/12 • Median time from 1st dose to off-study: 74.5 days

Additional Information

Rory Shallis, MD

Yale School of Medicine

Phone: (203) 200-4363

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60