Trial Title:
Iadademstat With Hypomethylating Agent in Patients With Myelodysplastic Syndrome
NCT ID:
NCT06502145
Condition:
Myelodysplastic Syndromes
Conditions: Official terms:
Preleukemia
Myelodysplastic Syndromes
Syndrome
Azacitidine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Azacitidine Level -1
Description:
Intravenous (IV) or subcutaneous (SC) 75 mg / m^2 days 1-7 X 28 days.
Arm group label:
Dose level -1
Other name:
Vidaza
Other name:
Onureg
Intervention type:
Drug
Intervention name:
Azacitidine Level 0
Description:
Intravenous (IV) or subcutaneous (SC) 75 mg / m^2 days 1-7 X 28 days.
Arm group label:
Dose level 0
Other name:
Vidaza
Other name:
Onureg
Intervention type:
Drug
Intervention name:
Azacitidine Level 1
Description:
Intravenous (IV) or subcutaneous (SC) 75 mg / m^2 days 1-7 X 28 days.
Arm group label:
Dose level 1
Other name:
Vidaza
Other name:
Onureg
Intervention type:
Drug
Intervention name:
Iadademstat Level -1
Description:
75 µg by mouth (PO) 5 days on, 2 days off for 2 weeks every 28 days.
Arm group label:
Dose level -1
Arm group label:
Maximum Tolerated Dose (MTD)
Intervention type:
Drug
Intervention name:
Iadademstat Level 0
Description:
75 µg PO 5 days on, 2 days off for 3 weeks every 28 days.
Arm group label:
Dose level 0
Arm group label:
Maximum Tolerated Dose (MTD)
Intervention type:
Drug
Intervention name:
Iadademstat Level 1
Description:
100 µg PO 5 days on, 2 days off for 3 weeks every 28 days.
Arm group label:
Dose level 1
Arm group label:
Maximum Tolerated Dose (MTD)
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).
Detailed description:
This is a single-arm, open-label phase 1 study designed to evaluate the safety of
iadademstat with azacitidine therapy. The trial will follow a 3+3 phase 1 dose-escalation
design.
First, three participants are given a low dose of the experimental treatment and
monitored for pre-specified toxicity events. If 0 participants experience one of these
toxicity events, then the next group of three participants is enrolled at a higher dose.
If two or three participants experience toxicity, then the next group of three
participants is enrolled at a lower dose (or the study ends). If one participant
experiences toxicity, another group of three participants is enrolled at the same dose
(hence the name, 3+3): if one or more of those participants experience toxicity, then the
dose is lowered for the next group of the study ends. Otherwise, if 0 of the additional
participants experience toxicity, the next group is enrolled at a higher dose.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female 18 years or older.
2. 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.
3. Intermediate, high, or very-high risk by the Revised International Prognostic
Scoring System (IPSS-R).
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (0-3 if
performance status is considered due to MDS).
5. Patient must have a body weight of at least 50 kg.
6. 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.
7. Patient is able to swallow oral medications.
8. Female subjects who:
1. Are postmenopausal for at least one year before the screening visit, OR
2. Are surgically sterile, OR
3. 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).
iii. Agree to not to donate or freeze egg(s) during the course of this study or
within 180 days after receiving their last dose of study drug.
9. Male subjects, even if surgically sterilized (i.e., status post vasectomy), who:
1. Agree to practice effective barrier contraception during the entire study
treatment period from the time of signing the informed consent through and
through six months after the last dose of study drug (female and male condoms
should not be used together), OR
2. 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 for the female partner]
withdrawal, spermicides only, and lactational amenorrhea are not acceptable
methods of contraception.)
3. Agree to not to donate or freeze sperm during the course of this study or
within 180 days after receiving their last dose of study drug.
10. Ability to provide informed consent or have a legally authorized representative
provide consent.
Exclusion Criteria:
A potential study subject who meets any of the following exclusion criteria is ineligible
to participate in the study:
1. 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.
2. 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.
3. 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.
4. Patient is on treatment with any investigational products within 3 weeks prior to
the first dose of study treatment.
5. Patient has had major surgery within 4 weeks prior to the first study dose.
6. 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.
7. Patients with known poorly controlled diabetes (glycosylated hemoglobin (HbA1c) ≥8%)
unless actively managed with appropriate therapy; patients with a history of
transient glucose intolerance due to corticosteroid administration may be enrolled
in this study if all other inclusion/exclusion criteria are met.
8. 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%.
9. Patients with known long QT Syndrome at screening.
10. History of allogeneic stem cell transplantation or CAR-T therapy within past 60
days.
11. 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.
12. Manifestations of malabsorption due to prior gastrointestinal (GI) surgery or GI
disease that may alter the absorption of iadademstat.
13. Pregnant or lactating / breastfeeding women.
14. 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.
15. Patient presents a known contraindication to any of the treatment drug excipients.
16. 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).
17. Patient is known to have human immunodeficiency virus infection. (HIV testing is not
required for eligibility assessment).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Froedtert Hospital & the Medical College of Wisconsin
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Contact:
Last name:
Guru Subramanian Guru Murthy, MD, MS
Email:
gmurthy@mcw.edu
Investigator:
Last name:
Guru Subramanian Guru Murthy, MD, MS
Email:
Principal Investigator
Start date:
October 2024
Completion date:
October 2027
Lead sponsor:
Agency:
Medical College of Wisconsin
Agency class:
Other
Source:
Medical College of Wisconsin
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06502145
