Health Condition 1: D469- Myelodysplastic syndrome, unspecified
Conditions
Interventions
Intervention1: HT-6184 2 mg capsule for 8 months (32 weeks) of Halia Therapeutics.: Dose: 2 mg,
Frequency: administration for 5 days followed by a 2 days drug holiday,
Route of Administration: Oral,
D
Sponsors
Halia Therapeutics
Eligibility
Inclusion criteria
Inclusion criteria: 1. Subjects greater than or equal to 18 years of age 2. Subject has signed the Informed Consent Form (ICF) and is able to comply with scheduled visits, treatment schedule, laboratory tests, bone marrow aspirates collection, biopsy and other protocol requirements. 3. Adequate organ function as defined by the following laboratory values a) Serum creatinine less than 2.0 X ULN b) AST and ALT less than 3.0 X ULN c) Total bilirubin less than 1.5 X ULN (or total bilirubin less than or equal to 3.0 x ULN with direct bilirubin within normal range only in subjects with well documented Gilberts syndrome or hemolysis or who required regular blood transfusions) 4. A documented diagnosis of MDS or non-proliferative (WBC less than 13,000 per micro L) myelodysplastic or myeloproliferative neoplasm (MDS or MPN) according to World Health Organization (WHO) 2022 classification and Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease (refer Appendix C) Following MDS subjects as per WHO 2022 criteria are eligible (refer Appendix D) MDS with low blasts and isolated 5q deletion (MDS-5q) MDS with low blasts and SF3B1 mutation (MDS-SF3B1) MDS with low blasts (MDS-LB) MDS, hypoplastic (MDS-h) MDS with increased blasts (MDS-IB) MDS-IB1 Following non-proliferative MDS or MPN subjects as per WHO 2022 criteria are eligible (refer Appendix E) Chronic myelomonocytic leukaemia Myelodysplastic or myeloproliferative neoplasm with neutrophilia Myelodysplastic or myeloproliferative neoplasm with SF3B1 mutation and thrombocytosis Myelodysplastic or myeloproliferative neoplasm, not otherwise specified 5. Less than 10 percent bone marrow myeloblasts 6. Refractory or intolerant of, or ineligible for treatment with an erythroid stimulating agent (ESA) as defined by any of the following a) Refractory to prior ESA treatment: Prior treatment with an ESA without response or no longer responding to an ESA alone or in combination with a myeloid growth factor (must have received recombinant erythropoietin (rHu EPO) with epoetin alfa greater than or equal to 40,000 IU per week for greater than 8 weeks or darbepoetin alpha 300-500 micro g Q 2-3 W for greater than 8 week b) Intolerant to prior ESA treatment Intolerant to prior ESA treatment with documentation of discontinuation due to intolerance or adverse event. c) ESA ineligible: Subject may be ESA ineligible due to low probability of response to ESAs based upon endogenous serum erythropoietin level greater than 200 U per L for subjects not previously treated with ESAs 7. Prior ESA treatment must have been discontinued greater than or equal to 2 weeks prior to date of study treatment 8. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2. (refer appendix A) 9. Subjects must have symptomatic anemia falling in any one of the below mentioned categories based on red blood cell (RBC) transfusion burden: a) Non-transfused, defined as patients having received no transfusions within 16 weeks of screening b) Low transfusion burden, defined as patients who received 3 to 7 units of RBCs within 16 weeks of screening, in at least 2 transfusion episodes (maximum 3 transfusions in 8 weeks) c) High transfusion burden, defined as patients who received 8 units of RBCs in 16 weeks, or 4 units of RBC i
Exclusion criteria
Exclusion criteria: 1. Other causes of anemia such as iron deficiency. Subjects must have documented marrow iron stores or serum ferritin >50 ng/ml. If marrow iron store is not available, the transferrin saturation must be > 20% or a serum ferritin > 50 ng/ mL. 2. Clinically significant anemia resulting from B12 or folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding. 3. Women must not be pregnant or breastfeeding. Females of childbearing potential should have a negative pregnancy test (sensitivity of at least 50 mIU/mL) within 28 days of first dosing and negative urine pregnancy test on day 1 of cycle 1. 4. Presence of concomitant intercurrent illness, or any condition which in the opinion of the Investigator, would compromise safe participation in the study, e.g. active severe infection, uncontrolled hypertension, uncontrolled seizure, unstable angina pectoris, new onset of exacerbation of a cardiac arrhythmia 5. Secondary MDS, defined as MDS that is known to have arisen as a result of chemical injury or treatment with chemotherapy and/or radiation for other diseases. 6. Treatment with cytotoxic chemotherapeutic agents or experimental agents for the treatment of MDS within 4 weeks of study treatment. 7. Chronic use of systemic corticosteroids for comorbid or study disease condition with in last 4 weeks of study treatment 8. Prior history of malignancy other than MDS (except non-melanoma skin cancer or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for > 3 years. 9. Subject has undergone a stem cell, bone marrow or solid organ transplant 10. Subjects with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV) and subjects with presence of viral load suggestive of active disease. 11. Prior treatment with disease modifying agents such as hypomethylating agents, or immunosuppressive therapy or experimental agents other than growth factor for MDS. 12. Participation in any clinical study within 90 days before the first dose of Investigational Product. 13. Loss of greater than or equal to 350 ml of blood within 90 days before the first dose of Investigational Product.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the efficacy of HT-6184 in subjects with lower risk MDS.Timepoint: 16 Weeks & 32 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1)To assess the effect of HT-6184 on biomarkers of inflammasome activation in MDS, & changes in clone size of somatic gene mutations 2) To explore potential enhancement of erythroid response by combined therapy of HT-6184 with an erythroid stimulating agent (ESA) 3) To monitor the adverse events & to ensure the safety of subjects after investigational product (IP) administration 4) To evaluate the Pharmacokinetic (PK) profile of HT-6184 in participants treated with HT-6184. Timepoint: 16 Weeks & 32 Weeks | — |
Countries
India, United States of America
Contacts
Public ContactDr Sandeep Singh
CBCC Global Research LLP
Outcome results
None listed