Clinical Trial 21887

• Overview

  Study Title:

  A Phase 1/2 Study of Active Myeloid Target Compound Combinations in MDS/MPN Overlap Syndromes

  Summary:

  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.

  Objective:

  Primary Phase 1: To characterize the DLTs of each novel oral targeted agent in combination with oral ASTX727 in order to determine the RP2D and schedule. Phase 2: To test whether the overall response to each novel ASTX727 combination therapy in MDS/MPN patients is sufficiently high to warrant further investigation in more definitive trials. Secondary To expand the safety analysis of each treatment combination in MDS/MPN patients. To assess the morphologic bone marrow response in MDS/MPN patients treated on each Arm of the study. To estimate the effect of each treatment combination on patient survival. To test the applicability of the proposed MDS/MPN IWG response criteria across multiple Arms of this study.

• Treatments

  Therapies:

  Chemotherapy (NOS)

  Medications:

  ASTX727 (); Itacitinib ()

• Inclusion Criteria

  Inclusion Criteria:
  • Must be 18 years of age or older at the time of signing the Informed Consent Form (ICF).
  • Must voluntarily sign the ICF and 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.
  • 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. 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.
  • 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.
  • Life expectancy of at least 3 months, as assessed by the treating physician.
  • For previously treated patients, recovery to Grade 1 or less, or baseline of any toxicities due to prior systemic treatments, excluding alopecia.
  • Must have adequate hepatic and renal function during screening.
  • Other criteria may apply.

• Exclusion Criteria

  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 include itacitinib (INCB039110) 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.
  • 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 (HSCT).
  • 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 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 abnormal electrocardiogram (ECG) or presence of abnormal screening ECG that, in the investigator's opinion, is clinically significant and contraindicated for clinical study. Corrected QT interval (QTc), as corrected by Fredericia, on screening EKG >500 milliseconds is excluded, unless there is concomitant right bundle branch block (RBBB) or concomitant left bundle branch block (LBBB) with a pacemaker.
  • Any known contraindications to the use of ASTX727.
  • Any sign of active and clinically significant bleeding.
  • Other active malignancy, not including localized non-melanoma skin cancer, cervical carcinoma in situ, breast ductal carcinoma in situ of the breast, or localized prostate cancer controlled with hormone therapy. Patients with history of other cancers should be free of disease without ongoing anti-neoplastic therapy for at least 2 years.
  • Receipt of wide-field radiotherapy (including therapeutic radioisotopes) ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study medications; or has not recovered from side effects of such therapy.
  • Patients who require continuation of a prohibited concomitant medication for which no alternative therapy or allowable substitute is available.
  • Active, uncontrolled infection. Patients with infection that is under control with active treatment are eligible.
  • Major surgery requiring general anesthesia within 4 weeks prior to starting study treatment.(Placement of a central line or port-a-catheter is acceptable within this time frame and does not exclude the patient.)
  • Women who are pregnant or lactating.
  • Subjects who expect to conceive or father children within the projected duration of the study and/or who are unwilling to use highly effective methods of contraception throughout the duration of the study, starting with the screening visit through the end of treatment visit. For women of child-bearing potential (WOCBP), a negative urine pregnancy test at screening and immediately prior to initiating treatment on any AM-001 treatment Arm (Cycle 1 Day 1) is required.
  • Other criteria may apply

If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.