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

NCT02979366 | Completed Phase 1 FDA Drug

• 3 other identifiers: CL1-64315-0012016-003768-38136541
• Study Type: interventional
• Target: 38
• Locations: 4 countries
• Sites: 9

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.

Conditions

Acute Myeloid Leukaemia (AML); Myelodysplastic Syndrome (MDS)

Outcome Measures

Primary Outcomes (5)

• 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 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

• Tolerability: Dose intensity

  From first dose until 30 days after the last dose administration

Secondary Outcomes (13)

• 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.

• Cumulative amount of a compound excreted in the urine (Ae)

  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

• 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.

• 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.

Study Arms (2)

S64315 (also referred as MIK665) administered once a week

EXPERIMENTAL

Drug: S64315 once a week

S64315 (also referred as MIK665) administered twice a week

EXPERIMENTAL

Drug: S64315 twice a week

Interventions

S64315 once a week DRUG

S64315 will be administered via i.v. infusion from 30 minutes and up to 3 hours once every week (21- day cycle), the starting dose is 50 mg. As data emerge during the study, the infusion duration and alternative dosing regimen may be changed.

Also known as: MIK665

S64315 (also referred as MIK665) administered once a week

S64315 twice a week DRUG

S64315 will be administered via i.v. infusion from 30 minutes and up to 3 hours twice every week (28- day cycle), the starting dose is 50 mg. As data emerge during the study, the infusion duration and alternative dosing regimen may be changed.

Also known as: MIK665

S64315 (also referred as MIK665) administered twice a week

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead
• ADIR, a Servier Group company: collaborator

Study Sites (9)

Patient Care Location: Smilow Cancer Hospital at Yale

New Haven, Connecticut, 06511, United States

Location

The University of Texas MD Anderson Cancer Center, Department of Leukemia, Division of Cancer Medicine

Houston, Texas, 77030, United States

Location

The Alfred Hospital Department of Haematology

Melbourne, 3004, Australia

Location

Royal Melbourne Hospital, Department of Clinical Haematology and BMT Service

Melbourne, 3050, Australia

Location

Institut Paoli-Calmettes Departement d'Hématologie

Marseille, 13009, France

Location

Hôpital Saint-Antoine Département d'Hematologie Clinique et de Thérapie cellulaire

Paris, 75012, France

Location

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, 31059 Cedex9, France

Location

Hospital Universitario Vall d' Hebron/VHIO Hematology Department

Barcelona, 08035, Spain

Location

Hospital Universitario La Fe Hematology Department

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Andrew WEI

  The Alfred Hospital, Melbourne, Victoria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: December 1, 2016
• Study Start: March 15, 2017
• Primary Completion: May 11, 2020
• Study Completion: May 11, 2020
• Last Updated: May 18, 2022

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Locations

US (2); AU (2); FR (3); ES (2)