Study of systemic Azacitidine chemotherapy in combination with or without APR-246 in patients with a type of Myelodysplastic Syndrome
- Conditions
- Myelodysplastic SyndromesMedDRA version: 20.0Level: HLTClassification code 10028536Term: Myelodysplastic syndromesSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002782-35-FR
- Lead Sponsor
- Aprea Therapeutics AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 154
1. Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements
2. Documented diagnosis of MDS, according to WHO classification (<20% blasts), that meets IPSS-R classification of intermediate, high, or very high-risk disease
3. Patient has adequate organ function as defined by the following laboratory values:
a) Creatinine clearance > 30 mL/min (by Cockcroft-Gault method; see Appendix IV)
b) Total serum bilirubin < 1.5 × ULN unless due to Gilbert’s Syndrome, underlying disease of MDS, hemolysis or considered an effect of regular blood transfusions
c) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN, unless due to underlying disease of MDS
4. Age =18 years at the time of signing the informed consent form (ICF)
5. Having at least one TP53 mutation which is not benign or likely benign
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
7. Females of childbearing potential: negative pre-treatment urine or serum pregnancy test
8. Females of childbearing potential and males with female partners of childbearing potential must be 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 116
1. Patient has a known history of HIV or active hepatitis B or active hepatitis C infection (testing not mandatory).
2. Patient has any of the following cardiac abnormalities (as determined by treating MD):
a) Myocardial infarction within six months prior to registration,
b) New York Heart Association Class III or IV heart failure (see Appendix III) or known left ventricular ejection fraction (LVEF) < 40%, as assessed by echocardiogram or MUGA scan;
c) A history of familial long QT syndrome,
d) Symptomatic atrial or ventricular arrhythmias not controlled by medications
e) QTc = 470 msec calculated from a mean of 3 ECG readings using Fridericia’s correction (QTcF = QT/RR0.33). Note: Patients with QTcF = 470 msec and with bundle branch block and/or pacemaker rhythm may be enrolled after approval by Medical Monitor.
3. 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.
4. Prior exposure to azacitidine, decitabine or investigational hypomethylating agent or induction chemotherapy for MDS or AML. Note: intensive chemotherapy for any other prior cancer is not exclusionary.
5. 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.
6. Concurrent use of erythroid stimulating agents, G-CSF, or GM-CSF within 14 days of the first day of study drug treatment.
7. History of allogeneic stem cell transplantation
8. Pregnancy: 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.
9.Active uncontrolled infection.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method