Clinical trial NCT04629443: Phase I/II Trial of S64315 Plus Azacitidine in Acute Myeloid Leukaemia
Official title: Phase I/II, International, Multicentre, Open-label, Non-randomised, Non-comparative, Study Evaluating the Safety, Tolerability and Clinical Activity of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Azacitidine in Patients With Acute Myeloid Leukaemia (AML)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukaemia
Keywords: Acute Myeloid Leukaemia
Oncology
Mcl-1 inhibitor
Azacitidine
Combination
Phase I/II
International
Safety
Maximum tolerated dose
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: ADIR, a Servier Group company
First posted: 2020-11-16
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Dose Limiting Toxicity (DLT) (Phase I - Dose Escalation)
timeFrame: Day -13 to Cycle 1 Day 28 (each cycle is 28 days)
measure: Number of Adverse Events (AEs) and Severe AEs (Phase I - Dose Escalation)
timeFrame: an average of 6 months
measure: Number of Serious Adverse Event (SAEs) and Fatal SAEs (Phase I - Dose Escalation)
timeFrame: Day -13 up to 30 calendar days after the patient's last study visit (an average of 6 months)
measure: Number of Participants With Dose Interruptions (Phase I - Dose Escalation)
timeFrame: Through study completion, an average of 6 months
measure: Number of Participants With Dose Reductions (Phase I - Dose Escalation)
timeFrame: Through study completion, an average of 6 months
measure: Dose Intensity for S64315 (Phase I - Dose Escalation)
timeFrame: Through study completion, an average of 6 months
measure: Dose Intensity for Azacitidine (Phase I - Dose Escalation)
timeFrame: Through study completion, an average of 6 months
Secondary outcomes:
measure: Assess Anti-leukemic Activity of S64315 in Combination With Azacitidine (Phase I - Dose Escalation)
timeFrame: Through study completion, an average of 6 months
measure: Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
timeFrame: Through study completion, an average of 6 months
measure: Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
timeFrame: Through study completion, an average of 6 months
measure: Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
timeFrame: Through study completion, an average of 6 months
measure: Assess Anti-leukemic Activity of S64315 in Combinaison With Azacitidine (Phase I - Dose Escalation)
timeFrame: Through study completion, an average of 6 months
measure: Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Area Under the Curve (AUC) (Phase I - Dose Escalation)
timeFrame: At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days)
measure: Pharmacokinetic Profile of S64315 Administered in Combination With Azacitidine in Plasma: Maximum Concentration (Cmax) (Phase I - Dose Escalation)
timeFrame: At Cycle 1 Day 2 and Cycle 1 Day 9 (each cycle is 28 days)
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center Department of Leukemia, Division of Cancer Medicine
state: Texas
city: Melbourne
country: Australia
facility: Victorian Comprehensive Cancer Centre
city: Melbourne
country: Australia
facility: The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Barcelona
country: Spain
facility: H. Universitario Valle de Hebrón Servicio de Hematología
city: Valencia
country: Spain
facility: H. Universitario La Fe Servicio de Hematologia
Study officials:
References: