Myelodysplastic Syndrome Clinical Trial
APR-246 & Azacitidine for the Treatment of TP53 Mutant Myelodysplastic Syndromes (MDS)
Summary
A Phase III, multicenter, randomized study to compare the rate of complete response (CR) and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone.
Full Description
A Phase III, multicenter, randomized study to compare the rate of CR and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone.
Treatment will be administered on an outpatient basis. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's disease.
Patients will be randomized (1:1) to one of two arms:
Experimental arm: APR-246 + azacitidine; or
Control arm: Azacitidine
Eligibility Criteria
Inclusion Criteria:
Signed Informed Consent (ICF) and is able to comply with protocol requirements
Documented diagnosis of MDS, according to World Health Organization (WHO) classification
Patient has adequate organ function as defined by the following laboratory values:
Creatinine clearance > 30 mL/min (by Cockcroft-Gault method)
Total serum bilirubin < 1.5 x Upper Limit of Normal (ULN) or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's Syndrome or hemolysis or who required regular blood transfusions
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN
Age ≥18 years at the time of signing the informed consent form (ICF)
Having at least one TP53 mutation which is not benign or likely benign
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
If of childbearing potential, negative pre-treatment urine or serum pregnancy test
If of childbearing potential (males and females), willing to use an effective form of contraception such as latex condom, hormonal birth control, intrauterine device or double barrier method during chemotherapy treatment and for at least six months thereafter
Exclusion Criteria:
Patient has a known history of human immunodeficiency virus (HIV) or active hepatitis B or active hepatitis C infection (testing not mandatory)
Patient has any of the following cardiac abnormalities (as determined by treating MD):
Myocardial infarct within six months prior to registration,
New York Heart Association Class II or worse heart failure (Appendix II) or known left ventricular ejection fraction (LVEF) < the institution lower limit of normal as assessed by echocardiogram
A history of familial long QT syndrome,
Clinically significant pericardial disease
Electrocardiographic evidence of acute ischemia
Symptomatic atrial or ventricular arrhythmias not controlled by medications
QTc ≥ 470 msec (QT cardiac interval)
Bradycardia (<40 bpm)
Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Patients with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g. cervix) may enroll irrespective of the time of diagnosis
Prior exposure to azacitidine, decitabine or investigational hypomethylating agent
Prior exposure to intensive chemotherapy
Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS within 14 days of the first day of study drug treatment
No concurrent use of erythroid stimulating agents
Patients with history of allogeneic stem cell transplantation
Pregnant women are excluded from this study because APR-246 has not been studied in pregnant patients. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with APR 246, breastfeeding should be discontinued if the mother is treated with APR-246.
Patients with active uncontrolled infections
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There are 26 Locations for this study
Duarte California, 91010, United States
Palo Alto California, 94304, United States
New Haven Connecticut, 06510, United States
Hollywood Florida, 33021, United States
Jacksonville Florida, 32224, United States
Tampa Florida, 12902, United States
Chicago Illinois, 60611, United States
Chicago Illinois, 60637, United States
Iowa City Iowa, 52242, United States
New Orleans Louisiana, 70121, United States
Baltimore Maryland, 21287, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02215, United States
Rochester Minnesota, 55902, United States
Saint Louis Missouri, 63130, United States
New York New York, 10065, United States
New York New York, 10065, United States
Cleveland Ohio, 44195, United States
Philadelphia Pennsylvania, 19104, United States
Pittsburgh Pennsylvania, 15232, United States
Nashville Tennessee, 37232, United States
Houston Texas, 77030, United States
Seattle Washington, 19023, United States
Nantes , 44093, France
Nice , 06000, France
Paris , 75010, France
Toulouse , 31100, France
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