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

Phase 1

Completed

• Conditions: Acute Myeloid Leukaemia
• Interventions: Drug: S 64315 (also referred as MIK665) and azacitidine

• Registration Number: NCT04629443
• Lead Sponsor: Institut de Recherches Internationales Servier

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-11-03
• Study First Submitted QC: 2020-11-13
• Study First Posted: 2020-11-16
• Study Start: 2021-02-17
• Primary Completion: 2023-08-25
• Study Completion: 2023-08-25
• Results First Submitted: 2024-03-29
• Status Verified: 2024-05
• Results First Submitted QC: 2024-05-09
• Last Update Submitted: 2024-05-09
• Results First Posted: 2024-06-06
• Last Update Posted: 2024-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

1. Patients aged ≥ 18 years
2. 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.
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
4. Adequate haematological, renal and hepatic functions based on the last assessment performed within 7 days prior to the first Investigational Medicinal Product administration.

Exclusion Criteria

1. Previous myeloproliferative syndrome (MPS).
2. Patients previously treated with any Mcl-1 inhibitor.
3. 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.
4. Severe or uncontrolled active acute or chronic infection.
5. Uncontrolled hepatitis B or C infection.
6. Known carriers of HIV antibodies, history of significant liver disease, active acute or chronic pancreatitis, active central nervous system disease.
7. Troponin > ULN (Upper Limit of reference range) or Troponin T > ULN if Troponin I cannot be assessed.
8. 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).
9. 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.
10. 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.
11. Uncontrolled arterial hypertension (systolic blood pressure (SBP) > 150 mmHg or diastolic blood pressure (DBP) > 95 mmHg).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
S64315 (also referred as MIK665) with azacitidine	S 64315 (also referred as MIK665) and azacitidine	-

Primary Outcome Measures

Name	Time	Method
Number of Adverse Events (AEs) and Severe AEs (Phase I - Dose Escalation)	an average of 6 months	Incidence and severity of AEs according to NCI CTCAE v5.0
Number of Serious Adverse Event (SAEs) and Fatal SAEs (Phase I - Dose Escalation)	Day -13 up to 30 calendar days after the patient's last study visit (an average of 6 months)	Incidence and severity of SAEs according to NCI CTCAE v5.0
Dose Limiting Toxicity (DLT) (Phase I - Dose Escalation)	Day -13 to Cycle 1 Day 28 (each cycle is 28 days)	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.
Dose Intensity for Azacitidine (Phase I - Dose Escalation)	Through study completion, 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

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Area Under the Curve (AUC) (Phase I - Dose Escalation)	At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days)
Assess Anti-leukemic Activity of S64315 in Combination With Azacitidine (Phase I - Dose Escalation)	Through study completion, an average of 6 months	Overall survival (OS)
Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)	Through study completion, an average of 6 months	Disease-free survival (DFS)
Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Maximum Concentration (Cmax) (Phase I - Dose Escalation)	At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days)

Trial Locations

Locations (7)

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

Victorian Comprehensive Cancer Centre; 🇦🇺 Melbourne, Australia

Hôpital Saint Antoine; 🇫🇷 Paris, France

Institut Paoli-Calmettes; 🇫🇷 Marseille, France

H. Universitario Valle de Hebrón Servicio de Hematología; 🇪🇸 Barcelona, Spain

H. Universitario La Fe Servicio de Hematologia; 🇪🇸 Valencia, Spain

The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services; 🇦🇺 Melbourne, Australia