Phase I/II Trial of S64315 Plus Azacitidine in Acute Myeloid Leukaemia

NCT04629443 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: CL1-64315-0042019-004896-38
• Study Type: interventional
• Target: 17
• Locations: 4 countries
• Sites: 7

Brief Summary

The purpose of this study is to assess the safety, tolerability and clinical activity of the combination S64315 with azacitidine in patients with acute myeloid leukaemia.

Conditions

Acute Myeloid Leukaemia

Keywords

Acute Myeloid Leukaemia; Oncology; Mcl-1 inhibitor; Azacitidine; Combination; Phase I/II; International; Safety; Maximum tolerated dose

Outcome Measures

Primary Outcomes (7)

• Dose Limiting Toxicity (DLT) (Phase I - Dose Escalation)

  Incidence of DLTs starting from the Lead-In Dose period to the end of the first cycle of treatment of S64315 in combination with azacitidine.

  Day -13 to Cycle 1 Day 28 (each cycle is 28 days)

• Number of Adverse Events (AEs) and Severe AEs (Phase I - Dose Escalation)

  Incidence and severity of AEs according to NCI CTCAE v5.0

  an average of 6 months

• Number of Serious Adverse Event (SAEs) and Fatal SAEs (Phase I - Dose Escalation)

  Incidence and severity of SAEs according to NCI CTCAE v5.0

  Day -13 up to 30 calendar days after the patient's last study visit (an average of 6 months)

• Number of Participants With Dose Interruptions (Phase I - Dose Escalation)

  Through study completion, an average of 6 months

• Number of Participants With Dose Reductions (Phase I - Dose Escalation)

  Through study completion, an average of 6 months

• Dose Intensity for S64315 (Phase I - Dose Escalation)

  Through study completion, an average of 6 months

• Dose Intensity for Azacitidine (Phase I - Dose Escalation)

  Through study completion, an average of 6 months

Secondary Outcomes (7)

• Assess Anti-leukemic Activity of S64315 in Combination With Azacitidine (Phase I - Dose Escalation)

  Through study completion, an average of 6 months

• Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)

  Through study completion, an average of 6 months

• Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)

  Through study completion, an average of 6 months

• Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)

  Through study completion, an average of 6 months

• Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)

  Through study completion, an average of 6 months

Study Arms (1)

S64315 (also referred as MIK665) with azacitidine

EXPERIMENTAL

Drug: S 64315 (also referred as MIK665) and azacitidine

Interventions

S 64315 (also referred as MIK665) and azacitidine DRUG

The combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) administered via intravenous (IV) infusion over at least 2 hours. During the combination treatment period S64315 will be administered according to a dose escalation scheme starting at 50 mg up to 250 mg might be explored. The schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen of azacitidine administered at 75 mg/m² via subcutaneous (SC) injection for 7 days from D1 to D7 of each cycle followed by a rest period of 21 days.

S64315 (also referred as MIK665) with azacitidine

Eligibility Criteria

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

You may qualify if:

• Patients aged ≥ 18 years
• Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization 2016 classification (Arber, 2016) excluding acute promyelocytic leukaemia (APL, French American-British M3 classification) with: relapsed or refractory disease and without established alternative therapy, or secondary to MyeloDysplastic Syndrome and without established alternative therapy or, newly diagnosed AML, not previously treated for AML and who are not candidate for intensive chemotherapy due to age or comorbidities.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Adequate haematological, renal and hepatic functions based on the last assessment performed within 7 days prior to the first Investigational Medicinal Product administration.

You may not qualify if:

• Previous myeloproliferative syndrome (MPS).
• Patients previously treated with any Mcl-1 inhibitor.
• Patients who have not recovered from toxicity of previous anticancer therapy, including Grade ≥ 2 toxicity (except alopecia of any grade) according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) version 5.0, prior to the first IMP administration.
• Severe or uncontrolled active acute or chronic infection.
• Uncontrolled hepatitis B or C infection.
• Known carriers of HIV antibodies, history of significant liver disease, active acute or chronic pancreatitis, active central nervous system disease.
• Troponin \> ULN (Upper Limit of reference range) or Troponin T \> ULN if Troponin I cannot be assessed.
• Clinically significant cardiac dysfunction (including New York Heart Association class ≥II heart failure, Left Ventricular Ejection Fraction (LVEF) \< 50% as assessed by echocardiography (ECHO) or Multi-Gated Acquisition (MUGA) scan).
• QT prolongation defined as QTc (QT interval corrected for heart rate) interval (corrected with Fridericia's formula) \> 450 ms for males and \> 470 ms for females, obtained from triplicate 12-lead ECG.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.
• Uncontrolled arterial hypertension (systolic blood pressure (SBP) \> 150 mmHg or diastolic blood pressure (DBP) \> 95 mmHg).

Sponsors & Collaborators

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

Study Sites (7)

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

Houston, Texas, 77030, United States

Location

Victorian Comprehensive Cancer Centre

Melbourne, 3002, Australia

Location

The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services

Melbourne, 3004, Australia

Location

Institut Paoli-Calmettes

Marseille, France

Location

Hôpital Saint Antoine

Paris, 75012, France

Location

H. Universitario Valle de Hebrón Servicio de Hematología

Barcelona, 08035, Spain

Location

H. Universitario La Fe Servicio de Hematologia

Valencia, 46026, Spain

Location

Related Links

• Find Results on Servier Clinical Trial Data website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasms

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Clinical Studies Department
• Organization: Institut de Recherches Internationales Servier (I.R.I.S.)

scientificinformation@servier.com

+33 1 55 72 60 00

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 16, 2020
• Study Start: February 17, 2021
• Primary Completion: August 25, 2023
• Study Completion: August 25, 2023
• Last Updated: June 6, 2024
• Results First Posted: June 6, 2024

Record last verified: 2024-05

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

AU (2); FR (2); US (1); ES (2)