Iadademstat With Hypomethylating Agent in Patients With Myelodysplastic Syndrome

NCT06502145 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PRO00053184
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study with a primary objective of determining the recommended phase II dose of iadademstat with azacitidine in adult subjects with myelodysplastic syndrome (MDS).

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose of Iadademstat.

  The dose identified in this trial that will be used in future clinical trials.

  Up to two years

Study Arms (4)

Dose level -1

EXPERIMENTAL

Dose level -1 will be considered only if there are dose-limiting toxicities at dose level 0. This is a regimen of azacitidine and iadademstat.

Drug: Azacitidine Level -1; Drug: Iadademstat Level -1

Dose level 0

EXPERIMENTAL

This is a regimen of azacitidine and iadademstat.

Drug: Azacitidine Level 0; Drug: Iadademstat Level 0

Dose level 1

EXPERIMENTAL

This is a regimen of azacitidine and iadademstat.

Drug: Azacitidine Level 1; Drug: Iadademstat Level 1

Maximum Tolerated Dose (MTD)

EXPERIMENTAL

The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a dose-limiting toxicity.

Drug: Iadademstat Level -1; Drug: Iadademstat Level 0; Drug: Iadademstat Level 1

Interventions

Azacitidine Level 1 DRUG

Intravenous (IV) or subcutaneous (SC) 75 mg / m\^2 days 1-7 X 28 days.

Also known as: Vidaza, Onureg

Dose level 1

Azacitidine Level 0 DRUG

Intravenous (IV) or subcutaneous (SC) 75 mg / m\^2 days 1-7 X 28 days.

Also known as: Vidaza, Onureg

Dose level 0

Iadademstat Level 1 DRUG

100 µg PO 5 days on, 2 days off for 3 weeks every 28 days.

Dose level 1; Maximum Tolerated Dose (MTD)

Iadademstat Level 0 DRUG

75 µg PO 5 days on, 2 days off for 3 weeks every 28 days.

Dose level 0; Maximum Tolerated Dose (MTD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female 18 years or older.
• Patients must have a diagnosis of myelodysplastic syndrome (MDS), or MDS / myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia (CMML) as defined by the World Health Organization (WHO) criteria.
• Intermediate, high, or very-high risk by the Revised International Prognostic Scoring System (IPSS-R).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (0-3 if performance status is considered due to MDS).
• Patient must have a body weight of at least 50 kg.
• Patient must meet the following screening clinical laboratory values as specified below:
• a. Hematologic: white blood cell (count) (WBC) below 30 x 109/L. Hydroxyurea can be used to achieve this level b. Hepatic: i. Total bilirubin ≤1.5 x upper limit of normal (ULN). Patients with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits.
• ii. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN.
• c. Renal: Serum creatinine ≤1.5 x ULN.
• Patient is able to swallow oral medications.
• Female subjects who:
• Are postmenopausal for at least one year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential:
• i. Agree to practice one highly effective method and one additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through six months after the last dose of study drug (female and male condoms should not be used together), OR ii. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception).

You may not qualify if:

• Prior therapy with hypomethylating agent or Lysine-specific histone demethylase 1A (LSD1) inhibitor. If patients were treated with any other agents having KDM1A/LSD1 inhibitory activity (such as tranylcypromine or phenelzine or similar drugs), they are only allowed if treatment finalized at least 3 weeks prior to first dose on study.
• Patient will require treatment while on study with concomitant drugs that target the 5- hydroxytryptamine2B (5-HT2B) receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline) except for drugs that are considered absolutely essential for the care of the patient and with appropriate treatment monitoring.
• Treatment with systemic antineoplastic chemotherapy within 14 days or 5 half-lives from the last dose - whichever is sooner - before Cycle 1, Day 1 of therapy. Radiation within 14 days before Cycle 1, Day 1 of therapy. The use of hydroxyurea for leukoreduction is permitted. Similarly, prior ESA, luspatarcept, or lenalidomide is allowed. Subjects must have recovered from the side effects of prior therapy per the treating physician's discretion.
• Patient is on treatment with any investigational products within 3 weeks prior to the first dose of study treatment.
• Patient has had major surgery within 4 weeks prior to the first study dose.
• Patients with uncontrolled hypertension (i.e., systolic blood pressure \>180 mm Hg, diastolic blood pressure \>95 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle 1, Day 1 is allowed.
• Patient has known active congestive heart failure New York Heart Association (NYHA) class 3 or 4 or patients with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 1 month prior to study entry demonstrates a left ventricular ejection fraction that is ≥40%.
• Patients with known long QT Syndrome at screening.
• History of allogeneic stem cell transplantation or CAR-T therapy within past 60 days.
• Patient has evidence of active uncontrolled viral, bacterial, or systemic fungal infection (i.e., no signs of severe systemic inflammatory response that makes patient clinically unstable in the opinion of the investigator, and patient is hemodynamically stable, with sustained body temperature under 38°C for 48-72 hours before starting study treatment and does not need oxygen supplementation or pressors to maintain blood pressure). Patients with uncontrolled infection shall not be enrolled until the infection is treated and brought under control.
• Manifestations of malabsorption due to prior gastrointestinal (GI) surgery or GI disease that may alter the absorption of iadademstat.
• Pregnant or lactating / breastfeeding women.
• Patient has any condition which, in the investigator's opinion, makes the patient unsuitable for study participation. For example, any inter-current illness or social situation that will limit compliance with study requirements. Any serious underlying medical or psychiatric condition (e.g., alcohol or drug abuse), dementia or altered mental status or any issue that would impair the ability of the patient to understand the informed consent form or that in the opinion of the investigator would contraindicate the patient's participation in the study or confound the results of the study.
• Patient presents a known contraindication to any of the treatment drug excipients.
• Patient has known active hepatic disorder or is known to be positive for hepatitis B or C infection with the exception of those with undetectable viral load within 3 months (Hepatitis B or C testing is not required for eligibility assessment).

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Guru Subramanian Guru Murthy, MD, MS

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 16, 2024
• Study Start: January 10, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)