NCT07283094 · Montefiore Medical Center
FHD-286 With Low-Dose Weekly Decitabine/Venetoclax in Patients With Acute Myeloid Leukemia
(FHD-286)
What this study is about
This is a Phase 1, uncontrolled, single-treatment group$1, where both patients and doctors know the treatment given, nonrandomized, gradually increasing doses, 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.
View original scientific description
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.
Interventions
DRUG
Decitabine
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
DRUG
Venetoclax
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
DRUG
FHD-286
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
Primary outcome measures
Dose-limiting toxicities (DLTs)
Time frame: Through the 12-week induction period
Dose limiting toxicity is defined as any adverse event (AE) that occurs during the DLT evaluation period that also meets any one of the criteria for hematologic and non-hematologic AEs as defined by the protocol and determined by the Data and Safety Monitoring Committee (DSMC), with input from the clinical study team. All AEs that cannot clearly be determined to be unrelated to FHD-286 or the combination of FHD-286 with DAC and VEN will be considered relevant to determining DLTs and any other emergent toxicities that are not explicitly defined by the DLT criteria to determine if any warrant a DLT designation, including toxicities that begin after the DLT evaluation period will be reviewed by the DSMC with input from the clinical study team. The percentage of participants with DLTs will be summarized by cohort.
Frequency and severity of the adverse event of special interest (AESI)
Time frame: Through the 12-week induction period
Differentiation syndrome is an adverse event of special interest for FHD-286. Suspected or confirmed differentiation syndrome will be reported, at minimum, as an important medical event. All Grade ≥2 events of Differentiation syndrome will be reported. The percentage of participants with DLTs will be summarized by cohort.
Percentage of participants who are able to continue treatment
Time frame: After 12-week induction period
The percentage of participants who are able to continue treatment without dose interruptions, reductions, or delays during the 12-week induction period will be summarized. Dose interruptions and delays are defined as delaying or interrupting treatment due to toxicity or intolerability for \>2 weeks.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Newly diagnosed adverse risk AML, including Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), per the 2022 ELN criteria, with a histopathologic diagnosis confirmed by hematopathology review OR AML that has progressed after 1 prior line of therapy with ≥5% blasts Inclusion Criteria 2 to 4 apply only for patients who are individuals with newly diagnosed AML:
- Aged ≥75 years, or aged 18-74 years and either refuse to receive intensive induction chemotherapy or are not a candidate for intensive induction chemotherapy due to one or more of the following comorbidities:
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or 3
- Cardiac history of congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina pectoris
- Diffusing capacity of the lung for carbon monoxide ≤65% or forced expiratory volume in 1 second ≤65%
- Creatinine clearance ≥30 mL/min to \<45 mL/min
- Moderate hepatic impairment with total bilirubin \>1.5 to ≤3.0×upper limit of normal (ULN)
- Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy
- Bone marrow blasts ≥10%
- Have not received a hypomethylating agent (HMA) or VEN for their disease under study
- No other disease-directed therapy, except hydroxyurea or cytarabine, and including experimental or investigational drug therapy, for at least 14 days before study entry
- New diagnosed AML:
- 75 years: ≤2
- 18 years to \<75 years: ≤3
- AML that has progressed after 1 prior line of therapy (Any age):
- 3 if R/R AML
- Life expectancy ≥3 months
- Adequate end organ function, defined as:
- Adequate hepatic function, including:
- Serum total bilirubin ≤3.0×ULN, unless considered due to advanced hematologic malignancy involvement or documented Gilbert syndrome with direct bilirubin ≤1.5×ULN
- Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase ≤3.0×ULN, unless considered due to advanced hematologic malignancy involvement
- Prothrombin time ≤1.5×ULN or international normalized ratio ≤1.4
- Activated partial thromboplastin time ≤1.5×ULN Note: Individuals who have been receiving a stable dose of anticoagulation therapy without bleeding episodes for ≥12 weeks may be considered for the study
- No known portal vein thrombosis
- Glomerular filtration rate (GFR) ≥30 mL/min (based on a contemporary, widely accepted, and clinically applicable equation that estimates GFR or a measure of GFR)
- Adequate cardiovascular, respiratory, and immune system function as evidenced by the below criterion and in the opinion of the investigator: a. Left ventricular ejection fraction (LVEF) of ≥40% by echocardiogram (ECHO)
- White blood cell count ≤20×10\^9/L (treatment with hydroxyurea or cytarabine ≤1 g/m2 to achieve this count is allowed before the start of study treatment and for up to 28 days after the start of study treatment)
- Agree to abide by dietary and other considerations required during the study
- Ability to understand and willingness to sign a written informed consent form and complete study-related procedures
Exclusion criteria
- Acute promyelocytic leukemia
- Core binding factor AML who is a candidate for intensive chemotherapy
- Eligible for and willing to receive standard HMA/VEN therapy (only applicable for individuals with newly diagnosed AML)
- Evidence (or suspicion) of central nervous system (CNS) involvement
- Prior treatment with azacitidine, DAC, VEN, or FHD-286. For individuals with AML that has progressed after 1 prior line of therapy, prior treatment with Azacitidine, Decitabine and VEN is allowed
- Currently pregnant or breast-feeding. Women of child-bearing potential (WOCBP) must have negative serum pregnancy test within 72 hours before treatment start. (NOTE: WOCBP is any biological female, regardless of sexual or gender orientation, having undergone tubal ligation, or remaining celibate by choice, who has not undergone a documented hysterectomy or bilateral oophorectomy or has had a menses any time in the preceding 12 months \[therefore not naturally post-menopausal for \>12 months\].)
- Planning to become pregnant within 1 year after start of study treatment
- Uncontrolled intercurrent illness that could limit life expectancy or ability to complete study correlates. This includes, but is not limited to:
- Ongoing or active infection. Because patients with myeloid malignancies are prone to infections, if individuals are actively being treated with appropriate antibiotics or antifungal agents with clinical evidence of infection control, they may be considered for the study. If treatment with a triazole antifungal agent is indicated, isavuconazonium sulfate should be used preferentially. If isavuconazonium sulfate cannot be used, a different triazole antifungal agent may be used. Refer to Exclusion Criterion 10a regarding strong Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors
- Uncontrolled concurrent malignancy
- Heart rate-corrected QT interval (QTc) by Fridericia method (QTcF) \>470 milliseconds (ms) or other factors that increase the risk of QTc prolongation. Participants with QTcF \>470 ms and bundle branch block and/or pacemaker rhythm may be considered for the study
- Congestive heart failure of New York Heart Association class III/IV. Individuals with compensated heart failure are permitted
- Unstable angina pectoris
- New or unstable cardiac arrhythmia. Patients with stable or controlled arrhythmias may be considered for the study.
- Decompensated liver cirrhosis (Child-Pugh score ≥12 or a Model for End-Stage Liver Disease (MELD) score ≥21)
- Psychiatric illness/social situation that would limit compliance with study requirements
- Any other prior or ongoing condition that, in the opinion of the investigator, could adversely affect the safety of the individual or impair the assessment of study results
- Unable to tolerate administration of oral medication or has gastrointestinal dysfunction that would preclude adequate absorption, distribution, metabolism, or excretion of FHD-286.
- Taking medications classified as:
- Strong CYP3A inhibitors. Individuals must have stopped treatment with strong CYP3A inhibitors at least 1 week or 5 half-lives, whichever is longer, before the first dose of study drug. Strong CYP3A inhibitors may be permitted; however, the FHD-286 dose should be reduced to 1.5 mg QD when a strong CYP3A inhibitor is in use, and for at least 1 week or 5 half-lives of the strong CYP3A inhibitor, whichever is longer, after the end of treatment with the strong CYP3A inhibitor. The venetoclax dose should be reduced as per the United States Prescribing Information (USPI)
- Strong CYP3A inducers. Individuals must have stopped treatment with strong CYP3A inducers at least 2 weeks or 5 half-lives, whichever is longer, before the first dose of study drug
- Sensitive CYP3A substrates with narrow therapeutic indices
- Taking proton pump inhibitors (PPIs). Administration of PPIs must be stopped or switched to another acid-reducing agent (e.g., antacids or H2 blockers) at least 7 days before study entry
- WOCBP sexually active with male partners and fertile males sexually active with WOCBP unwilling to agree to use dual contraceptive measures (i.e., hormonal or barrier method of birth control, abstinence, condom), beginning at the screening visit and continuing until 4 weeks after taking the last dose of DAC/VEN and 90 days after taking the last dose of FHD-286. Participants must agree to refrain from donating sperm/Ova from the screening visit through 90 days after the last dose of FHD-286
- Uncontrolled active HIV infection, as this will further increase the risk for opportunistic infections. However, individuals with HIV with undetectable viral load by polymerase chain reaction, without opportunistic infection, with Cluster of Differentiation 4 count (CD4) count \>200 cells/µL, and on a stable regimen of antiretroviral therapy would be eligible
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, unless the individual has a sustained viral response to HCV treatment or immunity to prior HBV infection
- Known allergy or hypersensitivity to any component of DAC, VEN, or FHD-286 formulations
Where
- The Bronx, New York
Collaborators
Foghorn Therapeutics Inc.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 3, 2026 · Source of record for eligibility and locations