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

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ClinicalTrials.gov Identifier: NCT02979366
Recruitment Status : Recruiting
First Posted : December 1, 2016
Last Update Posted : May 23, 2019
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( 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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukaemia (AML) Myelodysplastic Syndrome (MDS) Drug: S64315 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, International, Multicentre, Open-label, Non-randomised, Non-comparative Study of Intravenously Administered S64315, a Mcl-1 Inhibitor, in Patients With Acute Myeloid Leukaemia (AML) or Myelodysplastic Syndrome (MDS)
Actual Study Start Date : March 15, 2017
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020


Arm Intervention/treatment
Experimental: S64315 (also referred as MIK665) Drug: S64315
S64315 will be administered via i.v. infusion over 30 minutes 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.
Other Name: MIK665




Primary Outcome Measures :
  1. Incidence of DLTs during the first cycle of treatment with single agent S64315 [ Time Frame: 21-day cycle 1 ]
  2. Safety tolerance profile of S64315 assessed by:Incidence and severity of AEs [ Time Frame: From first dose until 30 days after the last dose administration ]
  3. Tolerability: Dose interruptions [ Time Frame: From first dose until 30 days after the last dose administration ]
  4. Tolerability: Dose reductions [ Time Frame: From first dose until 30 days after the last dose administration ]
  5. Tolerability: Dose intensity [ Time Frame: From first dose until 30 days after the last dose administration ]

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


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 < 25.1000000000 /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.

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)
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02979366


Contacts
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Contact: Institut de Recherches Internationales Servier Clinical Studies Department +33 1 55 72 43 66 clinicaltrials@servier.com

Locations
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United States, Connecticut
Patient Care Location: Smilow Cancer Hospital at Yale Recruiting
New Haven, Connecticut, United States, 06511
United States, Texas
The University of Texas MD Anderson Cancer Center, Department of Leukemia, Division of Cancer Medicine Recruiting
Houston, Texas, United States, 77030
Australia
The Alfred Hospital Department of Haematology Recruiting
Melbourne, Australia, 3004
Royal Melbourne Hospital, Department of Clinical Haematology and BMT Service Recruiting
Melbourne, Australia, 3050
France
Institut Paoli-Calmettes Departement d'Hématologie Recruiting
Marseille, France, 13009
Hôpital Saint-Antoine Département d'Hematologie Clinique et de Thérapie cellulaire Recruiting
Paris, France, 75012
Spain
Hospital Universitario Vall d' Hebron/VHIO Hematology Department Recruiting
Barcelona, Spain, 08035
Hospital Universitario La Fe Hematology Department Recruiting
Valencia, Spain, 46026
Sponsors and Collaborators
Institut de Recherches Internationales Servier
ADIR, a Servier Group company
Investigators
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Principal Investigator: Andrew WEI The Alfred Hospital, Melbourne, Victoria

Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site

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Responsible Party: Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier: NCT02979366     History of Changes
Other Study ID Numbers: CL1-64315-001
2016-003768-38 ( EudraCT Number )
First Posted: December 1, 2016    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask all interventional clinical studies in patients:

  • submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: http://clinicaltrials.servier.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions