Myelodysplastic Syndromes
Conditions
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).
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.
Interventions
DRUGAzacitidine Level -1
Intravenous (IV) or subcutaneous (SC) 75 mg / m\^2 days 1-7 X 28 days.
DRUGAzacitidine Level 0
Intravenous (IV) or subcutaneous (SC) 75 mg / m\^2 days 1-7 X 28 days.
DRUGAzacitidine Level 1
Intravenous (IV) or subcutaneous (SC) 75 mg / m\^2 days 1-7 X 28 days.
DRUGIadademstat Level -1
75 µg by mouth (PO) 5 days on, 2 days off for 2 weeks every 28 days.
DRUGIadademstat Level 0
75 µg PO 5 days on, 2 days off for 3 weeks every 28 days.
DRUGIadademstat Level 1
100 µg PO 5 days on, 2 days off for 3 weeks every 28 days.
Sponsors
Medical College of Wisconsin
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended phase II dose of Iadademstat. | Up to two years | The dose identified in this trial that will be used in future clinical trials. |
Countries
United States
Contacts
CONTACTMedical College of Wisconsin Cancer Center Clinical Trials Office
PRINCIPAL_INVESTIGATORGuru Subramanian Guru Murthy, MD, MS
Medical College of Wisconsin
Outcome results
None listed