FHD-286 With Low-Dose Weekly Decitabine/Venetoclax in Patients With Acute Myeloid Leukemia

Conditions

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Decitabine — DRUG
  Decitabine: 0.2 mg/kg/day subcutaneously once weekly (QW) (days 1, 8, 15, 22 \[±3 days\] of each 28-day cycle) \- A second weekly dose may be added if the investigator determines that more rapid debulking is required for a participant with high disease burden. The 2 weekly DAC doses should, preferably, be given on consecutive days
• Venetoclax — DRUG
  Venetoclax: 400 mg orally (PO) (tablets) QW, concurrent with the first weekly DAC dose (days 1, 8, 15, and 22 \[±1 day\] of each 28-day cycle) * Refer to the United States Prescribing Information (USPI) ("steady daily dose") for details regarding VEN dosage modifications. When decitabine is held, venetoclax should also be held. Based on best clinical judgment, the investigator may continue decitabine while withholding VEN for several doses to allow for improved count recovery * If treatment with a P-gp inhibitor or triazole antifungal agent classified as a moderate CYP3A inhibitor is medically necessary, reduce the VEN dose by at least 50% * If treatment with posaconazole is medically necessary, reduce the VEN dose to 70 mg * If treatment with another triazole antifungal agent classified as a strong CYP3A inhibitor is medically necessary, reduce the VEN dose to 100 mg
• FHD-286 — DRUG
  FHD-286: 2.5 or 5 mg (based on assigned dose group) PO (capsules) once daily (QD) 5 days/week (days 3-7, 10-14, 17-21, and 24-28 of each 28-day cycle) If acceptable safety and tolerability are observed at the end of cycle 1 with at least 3 DLT-evaluable participants in cohort 1 (FHD-286 2.5 mg QD), the dose of FHD-286 will be escalated to 5 mg QD for cohort 2. Doses of DAC and VEN will not change The 2 non-dosing days must be the day of and the day after the VEN dose * If necessary to improve tolerability and/or reduce toxicity, frequency of FHD-286 dosage may be reduced to 4 days/week * FHD-286 dose level will be escalated/de-escalated as described in protocol * If treatment with a strong CYP3A inhibitor is medically necessary, discussion with the PI is required and the FHD-286 dose should be reduced to 1.5 mg QD. Dose interruption or discontinuation of FHD-286 may also be necessary * See protocol for information on prohibited concomitant therapies when medically necessary

Study Details

This is a Phase 1, uncontrolled, single-arm, open-label, nonrandomized, dose escalation, study of Decitabine (DAC)+Venetoclax (VEN)+FHD-286 in participants with newly diagnosed Acute Myeloid Leukemia (AML) classified as adverse risk per the 2022 European Leukemia Net (ELN) criteria or AML that has progressed after one prior line of therapy.

Key Dates

Start date

Feb 3, 2026

Status verified

Feb 2026

Primary completion

May 31, 2028

Completion

Feb 28, 2030

Study Design

Enrollment

33 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Decitabine, Venetoclax, and FHD-286
  Administration: * Decitabine is reconstituted with 5 mL of sterile water and given by subcutaneous (SC) injection at the investigational site. * Venetoclax is taken as a tablet provided by the investigational site pharmacy or another authorized specialty pharmacy. * FHD-286 is taken as a capsule provided by the investigational site pharmacy.

Primary Outcome Measure

Dose-limiting toxicities (DLTs) [ Time Frame: Through the 12-week induction period ]

Central Contacts

• Mendel R Goldfinger, MD
  718-920-4826
  [email protected]
• Akash R Shah
  718-862-8840
  [email protected]

Locations (1)

Find similar trials in The Bronx, NY

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