Acute Myeloid Leukemia
Conditions
Brief summary
The primary purpose of Phase 1 is to characterize the safety and tolerability to identify the recommended dose (RD) of Debio 1562M for further development. The primary objective of Phase 2 is to evaluate the antileukemic activity of Debio 1562M.
Interventions
DRUGDebio 1562M
Administered as intravenous (IV) infusion
Sponsors
Debiopharm International SA
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For Phase 1-Dose escalation: Relapsed/refractory (R/R) AML (excluding acute promyelocytic leukemia) based on World Health Organization (WHO) Classification 2022 and relapsed/refractory higher-risk myelodysplastic syndrome (R/R HR -MDS) (includes high- and very high-risk MDS) as confirmed by the Revised International Prognostic Scoring System (IPSS-R) for whom no standard therapy of proven benefit is available. * For Phase1-Dose optimization and Phase 2: R/R AML (excluding acute promyelocytic leukemia) based on world health organization (WHO) classification 2022 for whom no standard therapy of proven benefit is available. * Eastern Cooperative Oncology Group performance (ECOG PS) status ≤2. * Previous treatment-related toxicities must be resolved to ≤Grade 1 (excluding alopecia). * Individuals with prior autologous or allogeneic bone marrow (BM) transplant are eligible. * Prior allogeneic transplant must meet the following conditions: the transplant must have been performed more than 120 days before the first administration of Debio 1562M, the participant must not have ≥Grade 1 active graft versus host disease (GvHD) at the time of trial treatment start and must be off all immunosuppression for at least 2 weeks prior to starting treatment with Debio 1562M. Steroid use \[equivalent to ≤20 milligrams (mg) prednisone\] before and during the trial is allowed as long as this is not being used as post-transplant immunosuppression or graft versus host disease (GVHD) directed therapy. * Adequate renal and hepatic function defined as: 1. Estimated glomerular filtration rate (eGFR) ≥60 milliliter per minute (mL/min) based on the chronic kidney disease-Epidemiology Collaboration based on creatinine (CKD-EPIcr) 2021 equation. 2. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN). 3. Serum total bilirubin level ≤1.5× ULN (for participants with Gilbert's syndrome or chronic blood transfusions, total bilirubin ≤3.0× ULN).
Exclusion criteria
* Any prior exposure to cluster of differentiation (CD) 37 targeting agents. * Clinically active infection including known active hepatitis B or C, human immunodeficiency virus infection, or cytomegalovirus or any other known concurrent infectious disease that, in the judgment of the Investigator, would make a participant inappropriate for enrollment into this trial (retesting not required). * Clinically significant cardiac dysfunction within 6 months before enrollment including New York Heart Association Class III or IV heart failure, uncontrolled angina, myocardial infraction, severe uncontrolled ventricular arrhythmias, QT interval corrected for HR according to Fridericia's formula (QTcF) \>470 ms. * Clinically significant and active cardiopulmonary disease. * Other malignancies, except of: 1. Hematologic malignancies other than those being investigated for which individuals are not on active antineoplastic therapy 2. Nonhematologic malignancies in remission and for which individuals must have completed all antineoplastic therapy at least 6 months before trial treatment start and all treatment-related toxicities must have resolved to ≤Grade 1. * Evidence for active central nervous system (CNS) leukemia involvement. If the participant has a prior history of CNS AML, the participant must have at least 2 negative cerebrospinal fluid (CSF) analyses and either a magnetic resonance imaging (MRI) or computed tomography (CT) (if MRI is not feasible) of the brain demonstrating no evidence of CNS disease. * Evidence of peripheral neuropathy Grade ≥2. * History of hypersensitivity to Debio 1562M (including its components), or any of its excipients. * Treatment with any antileukemic therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational agent within 14 days or within 5 half-lives of the investigational treatment prior to first dose of trial treatment, whichever is shorter. Hydroxyurea may be given prior to and after trial treatment start for control of leukocytosis. * Major surgery within 4 weeks prior to the start of treatment, or participant who have not recovered from side effects of the surgery. * Pregnancy or breastfeeding. Note: Other Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1 (Dose Escalation): Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | Up to Day 28 |
| Phase 1: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | Up to Day 219 |
| Phase 1 (Dose Optimization): Recommended Dose (RD) of Debio 1562M | Up to Day 198 |
| Phase 2: Percentage of Participants With Complete Remission (CR) + CR with partial hematological recovery (CRh) | Up to Day 198 |
Secondary
| Measure | Time frame |
|---|---|
| Phases 1 and 2: Overall Response (OR) | Up to Day 198 |
| Phases 1 and 2: Percentage of Participants with CR | Up to Day 198 |
| Phase 1: Percentage of Participants With CR+ CRh | Up to Day 198 |
| Phases 1 and 2: Percentage of Participants With Composite Complete Remission (cCR) | Up to Day 198 |
| Phases 1 and 2: Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplant (ASCT) | Up to Day 198 |
| Phases 1 and 2: Change From Baseline in Blood Blast Count | Baseline upto Day 198 |
| Phases 1 and 2: Duration of Remission (DOR) | Up to Day 198 |
| Phases 1 and 2: Relapse Free Survival (RFS) | Up to Day 198 |
| Phase 1 (Dose Optimization) and Phase 2: Event Free Survival (EFS) | Up to Day 198 |
| Phase 1 (Dose Optimization) and Phase 2: Overall Survival (OS) | Up to Day 198 |
| Phases 1 and 2: Plasma Concentration of Debio 1562M and its Metabolites | Pre-dose and at multiple time points up to Day 198 |
| Phase 1 (Dose Optimization) and Phase 2: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | Up to Day 219 |
Countries
United States
Contacts
CONTACTDebiopharm International S.A
Outcome results
None listed