Inclusion Criteria |
• At least 18 years of age and willing and able to meet all study requirements |
• Morphologically confirmed diagnosis of MDS/MPN, excluding juvenile myelomonocytic leukemia, according to the WHO (2016) diagnostic criteria |
• Treatment-naïve patients with no prior disease-modifying therapy may enroll in any AM-001 arm that is open to accrual in phase1b or phase 2 |
• After an appropriate wash-out period, patients who have failed or were intolerant to prior therapy regimens containing a DNMTi may enroll in any arm accruing in phase 1b or in the second stage of the phase 2 |
• Willing to undergo bone marrow biopsy with aspiration and tissue collection for disease assessment and correlative studies during screening and periodically throughout the trial |
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 |
• Life expectancy of at least 3 months |
• For previously treated patients, recovery to Grade ≤ 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia |
• Adequate hepatic and renal function during screening |
Exclusion Criteria |
• Patients will be excluded from arms that contain novel targeted agents to which they have prior exposure, with exception of ASTX727 |
• Prior receipt of any investigational therapy within 30 days or 5 half-lives before receiving the first dose of AM-001 study therapy |
• Prior receipt of any systemic non-investigational antineoplastic therapy, excluding hydroxyurea, within 21 days or 5 half-lives before receiving the first dose of AM-001 therapy |
• Known hypersensitivity to decitabine |
• Transformation to acute myeloid leukemia |
• Organ transplant recipients including allogeneic hematopoietic stem cell transplant |
• History of clinically significant or uncontrolled cardiac disease |
• History of abnormal EKG or presence of abnormal screening EKG that is clinically significant and contraindicated for clinical study |
• Known contraindications to use of ASTX727 |
• Active and clinically significant bleeding |
• Other active malignancy, excluding non-melanoma skin cancer, cervical carcinoma in situ, breast carcinoma in situ, or localized prostate cancer controlled with hormone therapy |
• Receipt of wide-field radiotherapy within 28 days or limited-field radiation within 14 days prior to initiating AM-001 treatment |
• Patients who require continuation of a prohibited concomitant medication |
• Active, uncontrolled infection |
• Major surgery requiring general anesthesia within 4 weeks prior to starting AM-001 therapy (other than placement/removal of vascular access devices) |
• Women who are pregnant or lactating |
• Women/men who expect to conceive/father children within the projected study period and/or who are unwilling to use highly effective methods of contraception throughout the study duration |
• Any concurrent serious or unstable medical or psychiatric condition that would jeopardize the patient’s ability to provide informed consent or to comply with the protocol |
• Any psychological, familial, geographical or sociological condition that would jeopardize the patient’s ability to comply with the study protocol |