The purpose of this first in human study is to assess safety, tolerability, Pharmacokinetic (PK) and preliminary clinical activity and to estimate the Maximum Tolerated Doses (MTD(s))/ Recommended Phase 2 Doses (RP2D(s)) of S65487 as single agent administered intravenously (i.v.) in adult patients with refractory or relapsed Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL), Multiple Myeloma (MM) or Chronic Lymphocytic Leukemia (CLL).
This study is designed in two parts: one part for dose escalation, one part for dose expansion.The dose escalation part will be followed by expansion part at the MTD(s)/RP2D(s) This study will utilize an adaptative Bayesian Logistic Regression model to guide dose escalation and estimate the MTD(s) based on the Dose Limiting Toxicity (DLT) relationship(s) for S65487 in the indications.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
S65487 is administered as single agent via i.v. infusion once a week on a 3-week cycle.
S65487 is administered in 3 to 5 i.v. infusions the first week of each cycle then once a week on the rest of the 3-week cycle.
The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services
Melbourne, Victoria, Australia
Centre Hospitalier Universitaire Régionale de Lille Hôpital Huriez
Lille, France
CHU Nantes Hôtel Dieu
Nantes, France
CHU de Nice - Hôpital l'Archet 1 Hématologie clinique
Nice, France
Clinica Universidad de Navarra
Madrid, Spain
Clínica Universidad Navarra- Servicio de Hematología
Pamplona, Spain
Hospital Clínico Universitario de Salamanca- Servicio de Hematología (4a planta)
Salamanca, Spain
Hospital Universitario La Fe - Servicio de Hematología - Torre F - Planta 7
Valencia, Spain
King's College Hospital NHS Foundation Trust
London, United Kingdom
The Christie NHS foundation Trust
Manchester, United Kingdom
...and 1 more locations
Incidence of Dose Limiting Toxicity (DLT)
Safety criterion
Time frame: until the end of the first cycle (each cycle is 21days)
Incidence and severity of Adverse Events
Safety and tolerability criteria
Time frame: through study completion an average of 6 months
Incidence and severity of Serious Adverse Events
Safety and tolerability criteria
Time frame: through study completion an average of 6 months
Number of participants with dose reductions
Time frame: through study completion an average of 6 months
Number of participants with dose interruptions
Time frame: through study completion an average of 6 months
Dose intensity
Time frame: through study completion an average of 6 months
The pharmacokinetic (PK) profile of S65487: Area Under the Curve (AUC)
Time frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)
PK profile of S65487: Volume of distribution at steady-state (Vss)
Time frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)
PK profile of S65487: total CLearance (CL)
Time frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)
PK profile of S65487: terminal half-life (t½z)
Time frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)
Best Overall Response (BOR)
Best Response observed during the treatment period
Time frame: Through study completion, an average of 6 months
Overall Response Rate (ORR)
Proportion of patients in whom a complete response (CR) or a partial response (PR)
Time frame: Through study completion, an average of 6 months
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