IRB Study Number 23-572
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
• To assess the safety and tolerability of R289 in subjects with LR MDS
Secondary Objectives
• To assess preliminary efficacy of R289 in subjects with LR MDS
• To characterize the pharmacokinetics (PK) of R835 and R466 in subjects with LR MDS*
Inclusion Criteria
Age
- Subject must be ≥ 18 years of age at the time of signing the informed consent.
Type of Subject and Disease Characteristics
Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System [IPSS]-R ≤ 3.5) (see Section 10.6) and ≤ 5% BM myeloblasts.
Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as TPOs, EPOs, luspatercept, and HMAs (i.e., azacytidine or decitabine). Subjects with del (5q) must have failed prior lenalidomide therapy.
Must meet at least one of the disease-related criteria for RBC transfusion or platelet count within 8 weeks prior to initial administration of study treatment:
a. Symptomatic anemia untransfused with hemoglobin < 9.0 g/dL within 8 weeks of registration, or red blood cell (RBC) transfusion dependent defined as receiving ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks in the preceding 16 weeks for a hemoglobin < 9.0 g/dL
b. Clinically relevant thrombocytopenia (platelet counts of < 100 × 109/L in at least 2 blood counts prior to study treatment and transfusion dependence)
All subjects must have documented marrow iron stores. If marrow iron stain is not available, the transferrin saturation must be > 20% or a serum ferritin > 100 ng/100 mL.
Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening.
Must have adequate organ function, defined as:
a. Hepatic function:
i. AST or ALT ≤ 1.5 × upper limit of normal (ULN)
ii. total bilirubin ≤ 1.5 × ULN
b. Renal function defined as creatinine clearance > 60 mL/min (using Cockcroft-Gault), or blood creatine < 1.5 mg/dL
Sex
Female subjects must be either postmenopausal for at least 1 year or surgically sterile; or, if of childbearing potential, must not be pregnant or lactating and must agree to use 2 highly effective methods of birth control throughout the duration of the trial and for 30 days following the last dose. Acceptable methods of birth control are defined in Section 10.4.
Male subjects must be willing to use adequate contraception, and to refrain from sperm donation, from the time of dosing until 90 days after the last dose of study treatment.
Informed Consent
- Willing and able to provide signed informed consent as described in Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria
Medical Conditions
Prior Treatment for MDS (i.e., TPOs, EPOs, luspatercept, HMAs) concluded < 4 weeks prior to study treatment.
Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding.
MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases.
Diagnosis of chronic myelomonocytic leukemia.
History of uncontrolled seizures.
Uncontrolled bacterial or viral infection (i.e., documented HIV, hepatitis B or hepatitis C).
History of an active malignancy within the past 2 years prior to study entry, with the exception of:
a. Adequately treated in situ carcinoma of the cervix uteri
b. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or
c. Any other malignancy with a life expectancy of more than 2 years
History of or active, clinically significant, cardiovascular, respiratory, GI, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator’s opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment.
Prior history of BM transplantation.
Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 480 milliseconds [msec]) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 1) using Fridericia’s QT correction formula.
History of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
Prior/Concomitant Therapy
Receiving any other concurrent chemotherapy, radiotherapy, or immunotherapy within 2 weeks of initiating study treatment, or the toxicity of the relevant prior treatment has not been resolved yet.
Use of concomitant medications that prolong the QT/QTc interval during study treatment (see Section 10.5.2).
Use of concomitant medications that are strong CYP3A or CYP2B6 inhibitors or inducers during study treatment (see Section 10.5.1).
Prior/Concurrent Clinical Study Experience
- Receipt of any other investigational agent or treatment within 2 weeks of initiating study treatment, or the toxicity of the relevant prior treatment has not been resolved yet.
Other Exclusions
- Unable or unwilling to cooperate with the Investigator for any reason.
