Phase I Study of S64315 Administred Intravenously in Patients With Acute Myeloid Leukaemia or Myelodysplastic Syndrome

Phase 1

Completed

• Conditions: Myelodysplastic Syndrome (MDS); Acute Myeloid Leukaemia (AML)
• Interventions: Drug: S64315 once a week; Drug: S64315 twice a week

• Registration Number: NCT02979366
• Lead Sponsor: Institut de Recherches Internationales Servier

Brief Summary

The CL1-64315-001 study is a phase I, international, multicentre, open-label, non-randomised, non-comparative study. This study is designed in two parts: one part for dose escalation, one part for dose expansion.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-11-18
• Study First Submitted QC: 2016-11-29
• Study First Posted: 2016-12-01
• Study Start: 2017-03-15
• Primary Completion: 2020-05-11
• Study Completion: 2020-05-11
• Status Verified: 2021-03
• Last Update Submitted: 2022-05-17
• Last Update Posted: 2022-05-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

• Male or female aged ≥ 18 years;

• Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML, excluding acute promyelocytic leukaemia (APL, French-American British M3 classification):

  • with relapsed or refractory disease without established alternative therapy or
  • secondary to MDS treated at least by hypomethylating agent or
  • > 65 years not previously treated for AML and who are not candidates for intensive chemotherapy nor candidates for established alternative chemotherapy Or Patients with cytologically confirmed and documented MDS), in relapse or refractory after previous treatment line including at least one hypomethylating agent and have ≥10% bone marrow blasts;

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

• Circulating white blood cells < 10^9 /L (with or without use of hydroxycarbamide).

• Adequate renal function defined as:

  • Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance (determined by MDRD) > 50 mL/min/1.73m2.

• LDH < 2 x ULN

• Adequate hepatic function defined as:

  • AST and ALT ≤ 1.5 x ULN
  • Total bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's syndrome (confirmed by the UGT1A1 polymorphism analysis), who are excluded if total bilirubin>3.0 x ULN or direct bilirubin > 1.5 x ULN

• Serum CK/CPK ≤2.5 x ULN.

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Exclusion Criteria

• Unlikely to cooperate in the study.
• Participant already enrolled in the study who has received at least one S64315 infusion.
• Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
• Participation in another interventional study requiring investigational treatment intake within 2 weeks or at least 5 half-lives (whichever is longer) prior to first dose of S64315 (participation in non-interventional registries or epidemiological studies is allowed).
• Presence of ≥ CTCAE grade 2 toxicity (except alopecia of any grade) due to prior cancer therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4.03)
• Unresolved ≥ CTCAE grade 2 diarrhoea or medical conditions associated with chronic diarrhoea (such as irritable bowel syndrome, inflammatory bowel disease)
• Known carriers of HIV antibodies
• Known history of significant liver disease
• Uncontrolled hepatitis B or C infection
• Known active or chronic pancreatitis
• History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
S64315 (also referred as MIK665) administered once a week	S64315 once a week	-
S64315 (also referred as MIK665) administered twice a week	S64315 twice a week	-

Primary Outcome Measures

Name	Time	Method
Tolerability: Dose interruptions	From first dose until 30 days after the last dose administration
Tolerability: Dose reductions	From first dose until 30 days after the last dose administration
Incidence of DLTs during the first cycle of treatment with single agent S64315	21-day cycle 1
Safety tolerance profile of S64315 assessed by:Incidence and severity of AEs	From first dose until 30 days after the last dose administration
Tolerability: Dose intensity	From first dose until 30 days after the last dose administration

Secondary Outcome Measures

Name	Time	Method
Area under the concentration-time curve from zero (time of drug administration) to tlast (AUC last) in plasma	D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Time corresponding to Clast (tlast) in plasma.	D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
total Clearance (CL)	D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Renal clearance (CLR)	only D1 of cycle 1
Preliminary efficacy assessment according to Cheson criteria (adapted for each disease)	From first dose until 30 days after the last dose administration
Concentration at the end of infusion (C inf) in plasma	D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Last quantifiable observed concentration (Clast) in plasma	D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Cumulative amount of a compound excreted in the urine (Ae)	only D1 of cycle 1
Area Under the Curve (AUC) in plasma	D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Terminal elimination half-life (t½,z) in plasma	D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Volume of distribution at steady-state (Vss) in plasma	D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Time corresponding to end of infusion (tinf/tend) in plasma	D1 and D2 of cycle 1 and 2, D15 and D16 of cycle 1 and D1 from cycle 3 to cycle 6.
Ae expressed as a percentage of the dose (fe) in urine	only D1 of cycle 1

Trial Locations

Locations (9)

The Alfred Hospital Department of Haematology; 🇦🇺 Melbourne, Australia

Royal Melbourne Hospital, Department of Clinical Haematology and BMT Service; 🇦🇺 Melbourne, Australia

Institut Paoli-Calmettes Departement d'Hématologie; 🇫🇷 Marseille, France

Hospital Universitario La Fe Hematology Department; 🇪🇸 Valencia, Spain

Institut Universitaire du Cancer Toulouse Oncopole; 🇫🇷 Toulouse, France

The University of Texas MD Anderson Cancer Center, Department of Leukemia, Division of Cancer Medicine; 🇺🇸 Houston, Texas, United States

Hospital Universitario Vall d' Hebron/VHIO Hematology Department; 🇪🇸 Barcelona, Spain

Hôpital Saint-Antoine Département d'Hematologie Clinique et de Thérapie cellulaire; 🇫🇷 Paris, France

Patient Care Location: Smilow Cancer Hospital at Yale; 🇺🇸 New Haven, Connecticut, United States