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Active Myeloid Target Compound Combinations in MDS/MPN Overlap Syndromes Overlap Syndromes (ABNL-MARRO)

ConditionMDS/MPN
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMichael Savona

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Patients treated with DNMTi therapy prior to enrollment in AM-001 who failed to achieve a complete remission, per the MDS/MPN IWG response criteria, after at least 4 cycles of DNMTi therapy

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • ASTX727

    Drug

    Taken by mouth daily during days 1-5 of every 28-day cycle.

  • Itacitinib

    Drug

    Taken by mouth daily during each 28-day cycle

  • Ruxolitinib

    Drug

    Dosage will be 5,15, or 20mg Taken by mouth BID for 28-day cycle

Treatment groups

94 Participants
are divided into 2 treatment groups
Group A: ASTX727 + itacitinibExperimental treatment 2 interventions
Group B: ASTX727 + ruxolitinibExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Phase 1: Determination of dose

Per CTCAE 5.0

Time frame
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

Time frame
Up to 2 years

Secondary outcomes

1

Adverse Event/DLT severity and frequency

Time frame
Up to 2 years
2

CR/MR rate defined as the proportion of patients who achieve either complete remission or marrow response as a best response to treatment.

Time frame
Up to 2 years
3

Overall survival (OS)

Defined as the time from first protocol-indicated treatment to death for any reason

Time frame
Up to 2 years
4

Progression free survival (PFS)

Defined as the time from first protocol-indicated treatment to disease progression or death for any reason

Time frame
Up to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Michael Savona

Lead sponsor

Vanderbilt-Ingram Cancer Center

Sponsor institution

Incyte Corporation

Collaborator

Theradex

Collaborator

Astex Pharmaceuticals, Inc.

Collaborator

Source ClinicalTrials.gov
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