Phase I Trial of AZD1775 and Belinostat in Treating Patients With Relapsed or Refractory Myeloid Malignancies or Untreated Acute Myeloid Leukemia

Stopped early · Phase 1

Conditions studied: Acute Myeloid Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Blast Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive, Myelodysplastic Syndrome, Recurrent Adult Acute Myeloid Leukemia, Recurrent Chronic Myeloid Leukemia, BCR-ABL1 Positive, Refractory Acute Myeloid Leukemia, Refractory Chronic Myeloid Leukemia, BCR-ABL1 Positive, Secondary Acute Myeloid Leukemia

In brief

This phase I trial studies the side effects and best dose of WEE1 inhibitor AZD1775 and belinostat when given together in treating patients with myeloid malignancies that have returned after a period of improvement or have not responded to previous treatment or patients with untreated acute myeloid leukemia. WEE1 inhibitor AZD1775 and belinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Key facts

Study ID

NCT02381548

Run by

National Cancer Institute (NCI)

People needed

20

Starts

2015-08-18

Expected to finish

2018-05-23

Last updated by the study team

2026-01-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have one of the following, histologically or cytologically confirmed:
• Acute myeloid leukemia (AML) [non- acute promyelocytic leukemia (APL) AML]
• If previously treated:
• AML that is relapsed or refractory to at least one prior line of therapy
• If previously untreated, must meet all of the following:
• >= 60 years of age
• Secondary or therapy-related AML
• Does NOT bear favorable cytogenetic and/or molecular features, eg, core-binding factor abnormalities, FLT3 Internal Tandem Duplication (FLT3-ITD) negative/NPM1 mutated, biallelic CCAAT/enhancer binding protein alpha (CEBPA) mutation without FLT3-ITD
• Chronic myeloid leukemia blast crisis (CML-BC)
• Relapsed or refractory to at least one Bcr-Abl-TKI-containing regimen
• Myelodysplastic syndrome (MDS), must meet all of the following:
• Higher risk MDS [intermediate-2 or high risk by the original International Prognostic Scoring System (IPSS)]
• Relapsed, refractory, or intolerant to at least one prior line of therapy containing hypomethylating agents (deoxyribonucleic acid [DNA] methyltransferase inhibitors)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
• Total bilirubin =< 1.5 × upper limit of normal (ULN) for the laboratory unless resulting from hemolysis
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × ULN for the laboratory
• Creatinine within normal limits for the laboratory OR creatinine clearance >= 60 mL/min/1.73 m\^2 (estimated glomerular filtration rate [eGFR]) for patients with creatinine levels above the ULN for the laboratory
• Human immunodeficiency virus (HIV)-infected persons are eligible if they meet other eligibility criteria including the following:
• No prior acquired immune deficiency syndrome (AIDS)-defining condition other than cluster of differentiation (CD)4+ cells nadir < 200/mm\^3
• Pre-leukemia CD4+ cell count >= 250/mm\^3
• Willing to adhere to antiretroviral therapy regimen with minimal overlapping toxicity and PK interactions with the experimental agents in this study; no zidovudine- and no ritonavir-containing regimens and no 3-drugs-in-1 pill regimens containing pharmacologic boosters are allowed; recommended regimens are integrase inhibitors combined with tenofovir and emtricitabine
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of AZD1775 and belinostat administration
• Ability to swallow medication
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if…

• Clinical picture indicative of leukostasis or evidence of disseminated intravascular coagulopathy
• Other investigational agent within 3 weeks prior to initiation of study therapy
• Ongoing toxicities >= grade 2 from prior therapy
• Acute promyelocytic leukemia (APL, M3)
• Active central nervous system (CNS) leukemia
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD1775 or belinostat
• Stem cell transplant within previous 3 months prior to initiation of study therapy
• Major surgical procedures =< 28 days before beginning study treatment or minor surgical procedures =< 7 day before beginning study treatment; no waiting required after placement of a vascular access device
• Uncontrolled infection
• Pregnant or nursing; women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study therapy
• Note: Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with AZD1775/belinostat
• Circulating blast count >= 50,000/uL within the week preceding enrollment
• Current candidacy for a potentially curative allogeneic stem cell transplant, unless declined
• Corrected QT (QTc) interval >= 450 ms (ie, grade 1 or higher) on electrocardiogram (ECG) prior to initiation of study treatment
• If baseline QTc on screening ECG is >= 450 ms (ie, grade 1 or higher):
• Check potassium and magnesium serum levels
• Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm QTc interval
• For patients with baseline heart rate (HR) < 60 beats per minute (bpm) or > 100 bpm, manual measurement of QT interval by cardiologist is required, with Fridericia correction applied to that manual measurement to determine the QTc for eligibility consideration
• Note: For patients with HR 60-100 bpm, manual measurement of QTc interval and use of Fridericia calculation is NOT required
• Any of the following related to risk of torsades de pointes and sudden cardiac death:
• History of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsades de pointes, or resuscitated cardiac arrest unless currently addressed with an implanted cardiac defibrillator
• Concomitant treatment with an anti-arrhythmic agent to prevent or control arrhythmia; agents used for rate-control of atrial fibrillation are permitted provided that they are not prohibited due to potential drug interactions
• Known congenital long QT syndrome
• Second degree atrioventricular (AV) block type II, third degree AV block, or ventricular rate < 50 bpm or > 120 bpm
• Unstable angina, myocardial infarction or New York Heart Association (NYHA) class III/IV congestive heart failure within 30 days preceding study enrollment

Where it is running

• Moffitt Cancer Center — Tampa, Florida, United States
• VCU Massey Comprehensive Cancer Center — Richmond, Virginia, United States

Full record on ClinicalTrials.gov

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