A study of HT-6184 in subjects with Myelodysplastic Syndrome (MDS) and Symptomatic Anemia.
- Conditions
- Health Condition 1: D469- Myelodysplastic syndrome, unspecified
- Registration Number
- CTRI/2023/11/059758
- Lead Sponsor
- Halia Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
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 with non-transfused hemoglobin less than 9.0 g per dL within 8 weeks of screening or red blood cell (RBC) transfusion-dependent defined as receiving greater than 3 units of PRBCs in the preceding 16 weeks of screening for a hemoglobin less than9.0g per dL.
10. NGS (Next-generation sequencing) myeloid specific somatic gene mutation profile where applicable with greater than or equal to 5 percent quantitation of clone size by variant allele frequency (VAF).
11. Women of child bearing potential, (defin
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).
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method