NCT03953898

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

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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). Olaparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVE: I. 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: I. 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: I. 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. V. 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.

Conditions

• Acute Myeloid Leukemia
• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Acute Myeloid Leukemia Post Cytotoxic Therapy
• Recurrent Acute Myeloid Leukemia
• Recurrent Myelodysplastic Syndrome
• Refractory Acute Myeloid Leukemia
• Refractory Myelodysplastic Syndrome

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
DRUG	Olaparib	Given PO

Timeline

• Start date: 2020-08-04
• Primary completion: 2024-01-16
• Completion: 2027-03-04
• First posted: 2019-05-17
• Last updated: 2026-04-13
• Results posted: 2025-03-30

Locations

11 sites across 1 country: United States

Regulatory

• FDA-regulated drug study