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

NCT03953898 | Active Not Recruiting Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2019-03057200002768610264UM1CA186689
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (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.

  Up to 6 cycles

Secondary Outcomes (5)

• ORR

  Up to 12 months

• Progression-free Survival (PFS)

  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

• Overall Survival (OS)

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

• Duration of Response (DOR)

  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

• Incidence of Adverse Events

  Up to 12 months

Other Outcomes (3)

• Change in 2-hydroxyglutarate (2HG) Levels

  Up to 12 months

• Minimal Residual Disease (MRD) Assessment

  Up to 12 months

• Mutant Allele Frequency

  Up to 12 months

Study Arms (1)

Treatment (olaparib)

EXPERIMENTAL

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. Patients also undergo bone marrow aspiration and collection of blood throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: Olaparib

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (olaparib)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (olaparib)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281

Treatment (olaparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

Location

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Wake Forest University at Clemmons

Clemmons, North Carolina, 27012, United States

Location

Wake Forest Baptist Health - Wilkes Medical Center

Wilkesboro, North Carolina, 28659, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Specimen Handling; olaparib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Results Point of Contact

• Title: Rory Shallis, MD
• Organization: Yale School of Medicine

rory.shallis@yale.edu

(203) 200-4363

Study Officials

• Rory M Shallis

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2019
• First Posted: May 17, 2019
• Study Start: August 4, 2020
• Primary Completion: January 16, 2024
• Study Completion (Estimated): March 4, 2027
• Last Updated: April 13, 2026
• Results First Posted: March 30, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (11)