Active Myeloid Target Compound Combinations in MDS/MPN Overlap Syndromes Overlap Syndromes (ABNL-… (NCT04061421) | Clinical Trial Compass
RecruitingPhase 1/2
Active Myeloid Target Compound Combinations in MDS/MPN Overlap Syndromes Overlap Syndromes (ABNL-MARRO)
United States94 participantsStarted 2021-11-24
Plain-language summary
ABNL-MARRO (A Basket study of Novel therapy for untreated MDS/MPN and Relapsed/Refractory Overlap Syndromes) is an international European-American cooperation providing the framework for collaborative studies to advance treatment of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and explore clinical-pathologic markers of disease severity, prognosis and treatment response.
ABNL MARRO 001 (AM-001) is an Open label, phase 1/2 study within the framework of the ABNL-MARRO that will test novel treatment combinations in MDS/MPN. Each Arm of AM-001 will test an active myeloid target compound in combination with ASTX727, an oral drug combining fixed doses of the DNA methyltransferase inhibitor (DNMTi) decitabine and the cytidine deaminase inhibitor E7727, also known as cedazuridine in a single tablet.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Must be ≥ 18 years of age at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF; and must be willing and able to meet all study requirements.
✓. Must have morphologically confirmed diagnosis of MDS/MPN, excluding JMML, in accordance with WHO (2016) diagnostic criteria (Appendix 1, Section 12.1).
✓. Treatment-naïve patients (patients who have had no prior disease-modifying therapy) may enroll in any AM-001 Arm that is open to accrual in phase 1 or phase 2. Treatment-naïve patients may have received recombinant erythropoietin, danazol, hydroxyurea or anagrelide, which are not considered to be disease-modifying therapy for the purpose of this study.
✓. After an appropriate wash-out period, patients who have failed (or were intolerant to) prior therapy with a regimen(s) containing a DNMTi may enroll in any Arm in phase 1b or any Arm which has met the criterion of the first Simon's Stage and are open to accrual in the second Simon's Stage in phase 2 (Error! Reference source not found.). Except in the first stage of the phase 2, there are no limits on number of prior therapies if the patient meets all other eligibility criteria. Previously treated patients include:
✓. Must be willing to undergo bone marrow biopsy with aspiration during screening and bone marrow aspiration with tissue collection for disease assessment and correlative studies periodically throughout the trial.
✓. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
What they're measuring
1
Phase 1: Determination of dose
Timeframe: Up to 28 days
2
Phase 2: Overall response rate (ORR). Overall response includes patients who achieve best response of CR, PR, MR, or CB as defined by the MDS/MPN IWG proposed response criteria
✓. Life expectancy of at least 3 months, as assessed by the treating physician.
✓. For previously treated patients, recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia.
Exclusion criteria
✕. Patients should be excluded from any treatment Arm that includes a novel targeted agent to which they have had previous exposure. Novel targeted agents in this study currently include itacitinib (INCB039110) and ruxolitinib (RUX) only, currently. Patients who have had prior exposure to ASTX727 therapy are not excluded, provided they meet all other eligibility criteria.
✕. Prior receipt of any investigational study drug, including treatment on any prior AM-001 Arm, within 30 days or 5 half-lives (whichever is shorter) before receiving the first dose of study drug in an Arm of AM-001, except if approved by the medical monitor.
✕. Prior receipt of any systemic antineoplastic therapy, including but not limited to prior DNMTi therapy, standard induction or cytotoxic chemotherapy (excluding hydroxyurea), or approved targeted agent within 21 days or 5 half-lives (whichever is shorter) before receiving the first dose of study drug in an Arm of AM-001.
✕. Known hypersensitivity to decitabine and ruxolitinib.
✕. Transformation to acute myeloid leukemia (e.g., \>20% myeloid blasts in bone marrow or \>20% circulating blasts in peripheral blood).
✕. Organ transplant recipients including allogeneic hematopoietic stem cell transplant.
✕. History of clinically significant or uncontrolled cardiac disease, including recent history (within 6 months) of unstable angina, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure, or clinically significant uncontrolled arrhythmia. Patients with history of atrial tachycardia and/or bradycardia that is well-controlled with medical management and/or pacemaker for at least 1 month before the first dose of study drug will be allowed.
✕. History of thromboemobolic events (such as deep vein thrombosis, pulmonary embolism, stroke, myocardial infraction) in the 6 months prior to study entry.