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Acute Myeloid LeukemiaPhase 2NCT03953898

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

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Olaparib in people with Acute Myeloid Leukemia and Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, run by National Cancer Institute (NCI) at 11 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase II trial studies how well olaparib works in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory), or myelodysplastic syndrome. Patients must also have a change in the gene called the IDH gene (IDH mutation). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Olaparib
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
11 sitesUnited States
Study dates
4 Aug 2020to 4 Mar 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of olaparib in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
  • Diagnosis of MDS or AML per World Health Organization 2016 classification. AML may be de novo, or following a prior hematologic disorder, including MDS or Philadelphia chromosome-negative myeloproliferative neoplasm, and/or therapy-related.
  • Patients must have a documented IDH1 or IDH2 mutation within 30 days of inclusion based on mutational testing. Only specific mutations that lead to a neomorphic phenotype will be eligible for enrollment, and include those listed below:
  • IDH1: R132V, R132G, R132S, R132L, R132C and R132H
  • IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K.
  • Patients with AML or MDS should have disease that has relapsed after, or is refractory to, first-line therapy, with or without subsequent additional therapy.
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  • Patients with MDS should have at least a MDS-excess blasts (EB)1 at the inclusion and have a revised International Prognostic Symptom Score risk stratification of intermediate, high, or very high risk.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Patients may or may not have been previously treated with IDH targeted therapies.
  • Patients who have undergone allogeneic stem cell transplant (alloSCT) are eligible if they are >= 180 days from stem cell infusion, have no evidence of graft versus host disease (GVHD) > grade 1, and are >= 2 weeks off all immunosuppressive therapy.
  • Previous cytotoxic chemotherapy must have been completed at least 3 weeks and radiotherapy at least 2 weeks prior to Day 1 of treatment on the study, and all adverse events (AEs) (excluding alopecia) due to agents administered more than 4 weeks earlier should have recovered to < grade 1. Patients with hematologic malignancies are expected to have hematologic abnormalities at study entry. Hematologic abnormalities that are thought to be primarily related to leukemia are not considered to be toxicities (AEs) and do not need to resolve to < grade 1.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >= 60%).
  • Patient must have recovered from toxicities of any prior treatment regimen (no Common Terminology Criteria for Adverse Events [CTCAE] grading over 1 for non-hematological toxicities, return to baseline for hematological values).
  • Ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity may have a close relative, guardian, caregiver, or legally authorized representative consent on their behalf.
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless considered due to Gilbert's syndrome (measured within 28 days prior to administration of study treatment).
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless considered due to organ leukemic involvement (measured within 28 days prior to administration of study treatment). If liver metastases are present in which case they must be =< 5 x ULN.
  • Creatinine clearance of > 30 ml/min (measured within 28 days prior to administration of study treatment).
  • Patients are eligible for this study if low blood count and transfusion support are due to the MDS/AML.
  • Patients must have, in the best estimate of the treating physician, a life expectance of at least 12-16 weeks.
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  • Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50
  • Radiation-induced oophorectomy with last menses > 1 year ago
  • Chemotherapy-induced menopause with > 1 year interval since last menses
  • Surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential.

Who cannot join

  • Patients with acute promyelocytic leukemia.
  • Patients with active central nervous system (CNS) leukemia or requiring maintenance intrathecal chemotherapy.
  • Patients receiving concurrent chemotherapy, radiation therapy, or immunotherapy for AML/MDS.
  • Patients actively receiving any other investigational agents.
  • Management of treatment for patients with co-occurring mutations, like FLT3, will be prioritized by the treating physician after discussion of treatment options with the patient.
  • Hyperleukocytosis with > 50,000 white blood cell (WBC)/mcl. Hydroxyurea for WBC count control is permitted before starting treatment and may be continued until day 28 of cycle 1. The maximum dose of hydrea will be 6 grams per day. Patients will be withdrawn from the study if > 50,000 WBC/mcl occur or recur > 14 days after starting treatment on the study.
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  • Active, uncontrolled infection. Patients with infection controlled with antibiotics are eligible.
  • Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
  • Patients who are pregnant or nursing. Pregnant women are excluded from this study because olaparib is a PARP inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with olaparib, breastfeeding should be discontinued if the mother is treated with olaparib. These potential risks may also apply to other agents used in this study.
  • Resting electrocardiogram indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT by Fridericia's formula (QTcF) prolongation > 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
  • Patients with symptomatic uncontrolled CNS disease. Imaging to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
  • The patient can receive a stable dose of corticosteroids, up to 20 mg by mouth (PO) prednisone daily, before and during the study as long as these were started at least 4 weeks prior to treatment.
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Any previous treatment with PARP inhibitor, including olaparib.
  • Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
  • Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
  • Patient with active malignancies requiring active treatment that interferes with protocol therapy and/or with significant risk of clinical relapse within 12 months that would require treatment interfering with protocol therapy are excluded.
  • Persistent toxicities (> Common Terminology Criteria for Adverse Event [CTCAE] grade 2) caused by previous cancer therapy, excluding alopecia.
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment.
  • Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks. Patients without reasonable alternative may be included in the trial after discussion with the medical monitor.
  • Previous double umbilical cord blood transplantation (dUCBT).
  • Breast feeding women.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Wake Forest University at Clemmons

    Clemmons, North Carolina, 27012

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Yale University

    New Haven, Connecticut, 06520

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • Wake Forest Baptist Health - Wilkes Medical Center

    Wilkesboro, North Carolina, 28659

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: The PRIME Trial: PARP Inhibition in IDH Mutant Effectiveness Trial. A Phase II Study of Olaparib in Isocitrate Dehydrogenase (IDH) Mutant Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome

This phase II trial studies how well olaparib works in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory), or myelodysplastic syndrome. Patients must also have a change in the gene called the IDH gene (IDH mutation). Olaparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the rate of complete response (CR) to olaparib using a composite CR endpoint (CR + CR with incomplete hematologic response [CRi] + CR with partial hematologic response [CRh]) in subjects with isocitrate dehydrogenase (IDH)1/2 mutant myelodysplastic syndrome (MDS) or IDH1/2-mutant acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

  1. To determine the overall response rate (ORR) to olaparib using a composite ORR endpoint (CR + morphologic leukemia-free state [MLFS] + partial response [PR]) in patients with IDH mutant AML or MDS treated with olaparib.

II. To establish the progression free survival (PFS) of patients with IDH mutant AML or MDS treated with olaparib.

III. To determine the overall survival (OS) of patients with IDH mutant AML or MDS treated with olaparib.

IV. To establish the duration of response (DOR) to treatment with olaparib. V. To evaluate the safety and tolerability of olaparib in AML or MDS patients.

EXPLORATORY OBJECTIVES:

  1. To establish a relationship between treatment response and correlative studies such as plasma and bone marrow 2-hydroxyglutarate (2HG) levels, and IDH variant allele frequency.

II. To evaluate persistence of double strand breaks in IDH 1/2 mutant AML or MDS.

III. To evaluate response to therapy in the different IDH mutant genotypes.

IV. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), ribonucleic acid (RNA) sequencing (RNAseq) order to:

IVa. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned.

IVb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.

  1. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.

VI. To bank blood and bone marrow aspirate obtained from patients at the EET Biobank at Nationwide Children's Hospital.

OUTLINE:

Patients receive olaparib orally (PO) twice daily (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. Patients also undergo bone marrow aspiration and collection of blood throughout the study.

After completion of study treatment, patients are followed up at 90 days and then every 3 months until death.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Olaparib
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • OlaparibDrug

    Also called AZD 2281, AZD-2281, AZD2281, KU 0059436

    Given PO

Study groups in NCT03953898
Study groupRoleWhat they receive
Treatment (olaparib)ExperimentalPatients 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. Patients also undergo bone marrow aspiration and collection of blood throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: Olaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cumulative Overall Response Rate (ORR)

    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.

    Measured: Up to 6 cycles

Secondary outcomes (5)

  1. ORR

    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.

    Measured: Up to 12 months

  2. Progression-free Survival (PFS)

    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.

    Measured: 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

  3. Overall Survival (OS)

    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.

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

  4. Duration of Response (DOR)

    Measured: 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

  5. Incidence of Adverse Events

    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.

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2019
  2. Study start4 Aug 2020
  3. Primary completion16 Jan 2024
  4. Study completion4 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03953898
Sponsor's protocol ID
NCI-2019-03057
Other IDs
NCI-2019-03057, 2000027686, 10264, 10264, UM1CA186689
Status last verified
Sep 2026
First submitted
16 May 2019
Last updated
10 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Olaparib in people with Acute Myeloid Leukemia and Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, run by National Cancer Institute (NCI) at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative Overall Response Rate (ORR) (time frame: Up to 6 cycles). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03953898.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.

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