Phase 1/ Phase 2 Study to Assess Safety and Efficacy of Orally Administered JBI-802 in Subjects with Myeloproliferative Neoplasms (MPN) and Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) with Thrombocytosis.
- Conditions
- Myeloproliferative Neoplasms (MPN)Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)Essential Thrombocythemia (ET)Cancer - ThrombocythaemiaCancer - BoneCancer - Leukaemia - Chronic leukaemiaBlood - Haematological diseases
- Registration Number
- ACTRN12624000478516
- Lead Sponsor
- Jubilant Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 30
- Male or female subjects aged greater than 18 years at the time of screening visit.
For Dose Escalation Phase: Subjects diagnosed with any one of the following:
• Subject with diagnosis of Essential Thrombocythemia (ET) per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms.
• Subject requires treatment in order to lower platelet count based on subject age over 60 or history of thrombosis.
• Subject with Morphologically confirmed diagnosis of MDS/MPN neoplasms, excluding Juvenile Myelomonocytic Leukaemia (JMML), CMML and aCML (Atypical Chronic Myeloid Leukaemia), in accordance with WHO 2016 revised criteria, that is relapsed and/or refractory or intolerant to standard of care and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits.
• Subject with Myelodysplastic/myeloproliferative neoplasm.
For Dose Expansion Phase
Subjects diagnosed with any one of the following:
• Subject with diagnosis of Essential Thrombocythemia (ET) per WHO diagnostic criteria for myeloproliferative neoplasms which requires treatment in order to lower platelet count based on subject age over 60 or history of thrombosis.
• Subject with diagnosis of Polycythemia Vera (PV) per WHO diagnostic criteria that is relapsed and/or refractory or intolerant to standard of care and that, in the opinion of the Investigator,subjects
who have no available therapies known to provide clinical benefits.
•Subject with morphologically confirmed diagnosis of pre-fibrotic myelofibrosis (MF) subject in accordance with the WHO 2016 revised criteria, that is relapsed, intolerant, and/or refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits.
1. MDS/MPN (MDS/MPN-RS-T, MDS/MPN unclassifiable and CMML subjects providing the marrow blast count is less than or equal to 5%.).
2. Subject must have disease that failed at least one standard therapy or being intolerant to standard of care.
3. Subject must have discontinued immediate prior therapy at least 1 week (4 weeks for interferon) prior to study drug administration.
4. Subject with screening laboratory values:
• Hb greater or equal to 9 g/dL, if subject is transfused to meet this criterion, transfusion must be completed greater or equal to 14 days prior to first dose.
• Absolute neutrophil count greater or equal to 1500 × 10^9/L
• Absolute neutrophil count greater or equal to 1000 × 10^9/L, if significant marrow infiltration
• Platelet count greater or equal to 450 × 10^9/L for dose finding
• Platelet count greater or equal to 100 × 10^9/L for expansion cohort at RP2D, if subject is transfused to meet this criterion, transfusion must be completed greater or equal to 14 days prior to first dose
• Total bilirubin less than or equal to 1.5 × ULN. Subjects with Gilbert’s syndrome may be enrolled with up to 3.0 × ULN
• Aspartate transaminase (AST) and Alanine transaminase (ALT) less than or equal to 2.5 × ULN
• Calculated creatinine clearance (CrCL) greater or equal to 30 mL/min (Cockcroft-Gault formula)
• Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT) less than or equal to 1.5 × ULN, if subject is not anticoagulated (Note: If subject is on anticoagulants, the subject must be on a stable dose for at least 2 weeks prior to screening)
5. Subject with resolution of any clinically significant toxic effects of prior t
1. Subject who is treated with systemic anticancer therapy or biological therapy or an investigational agent within 2 weeks or 5 half-lives, whichever is shorter, prior to start of study drug treatment.
• For MF subject who come off JAK2 antagonists or hydroxyurea, shorter washout is permitted as these subject progress quickly after treatment discontinuation and remain eligible (steroids must be stop at least 7 day before start of study drug treatment)
• Subject who is in need of immediate cytoreduction should be excluded
2. Subject who has undergone autologous/allogeneic Haematopoietic Stem Cell Transplantation (HSCT) therapy within 60 days of the first dose of study drug, or subject on immunosuppressive therapy post-HSCT at the time of screening, or currently with clinically significant Graft-Versus- Host Disease (GVHD) as per treating physician (subjects in relapse after allogeneic transplantation must be off treatment with systemic immunosuppressive agents for at least 4 weeks prior to screening.
3. Subject with major surgery less than or equal to 21 days prior to starting study drug or has not recovered from adverse effects of such procedure.
4. Subject who underwent surgery (e.g., stomach bypass) or medical condition that might significantly affect absorption of medicines.
5. Subject who underwent radiotherapy within 2 weeks prior to start of study drug treatment (palliative radiation or stereotactic radiosurgery within 7 days prior to start of study treatment). Subjects must have recovered from all radiotherapy-related toxicities.
6. Subject with known malignant central nervous system disease other than neurologically stable, treated brain metastases– defined as metastasis having no evidence of progression or hemorrhage for at least 4 weeks after treatment (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of symptomatic brain metastases for at least 14 days prior to enrollment.
7. Subject with severe or unstable medical condition, such as congestive heart failure ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an uncontrolled cardiac arrhythmia requiring medication ( less than or equal to Grade 2, according to NCI CTCAE Version 5), myocardial infarction within 6 months prior to starting study treatment, or any other significant or unstable concurrent cardiac illness.
8. Subject with congenital long QT syndrome or corrected QT interval by Fridericia (QTcF interval) greater than 450 msec for males and greater than 470 msec for females at screening.
9. Subject with history of other previous or concurrent cancer that would interfere with the determination of safety or efficacy assessments with respect to the qualifying solid tumor malignancy.
10. Subject with live vaccines within 30 days prior to the first dose of JBI-802.
11. Subjects who receive Glucocorticoids for any purpose other than to modulate symptoms from an event of clinical interest or for use as a premedication in participants with a known history of an IV contrast allergy administered as part of CT radiography.
12. Bisphosphonates and/or receptor activator of nuclear factor kappa-B ligand inhibitor therapies cannot be initiated after the Informed Consent Document(s) has been signed. These therapies may be continued if treatment with an agent from 1 of these 2 classes was initiated prior to signing the Informed Consent Document(s).
13. Subject with
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method