Description:
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.
Title
- Brief Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
CL1-64315-004
- SECONDARY ID:
2019-004896-38
- NCT ID:
NCT04629443
Conditions
Interventions
Drug | Synonyms | Arms |
---|
S 64315 (also referred as MIK665) and azacitidine | | S64315 (also referred as MIK665) with azacitidine |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
S64315 (also referred as MIK665) with azacitidine | Experimental | | - S 64315 (also referred as MIK665) and azacitidine
|
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).
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Dose Limiting Toxicity (DLT) (Phase I - dose escalation) |
Time Frame: | Day -13 to Cycle 1 Day 28 (each cycle is 28 days) |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Assess anti-leukemic activity of S64315 in combinaison with azacitidine (Phase I - dose escalation) |
Time Frame: | Through study completion, an average of 6 months |
Safety Issue: | |
Description: | Overall survival (OS) |
Measure: | Assess anti-leukemic activity of S64315 in combinaison with azacitidine (Phase I - dose escalation) |
Time Frame: | Through study completion, an average of 6 months |
Safety Issue: | |
Description: | Duration of response (DOR) |
Measure: | Assess anti-leukemic activity of S64315 in combinaison with azacitidine (Phase I - dose escalation) |
Time Frame: | Through study completion, an average of 6 months |
Safety Issue: | |
Description: | Best overall response (BOR) |
Measure: | Assess anti-leukemic activity of S64315 in combinaison with azacitidine (Phase I - dose escalation) |
Time Frame: | Through study completion, an average of 6 months |
Safety Issue: | |
Description: | Progression-free survival (PFS) |
Measure: | Assess anti-leukemic activity of S64315 in combinaison with azacitidine (Phase I - dose escalation) |
Time Frame: | Through study completion, an average of 6 months |
Safety Issue: | |
Description: | Disease-free survival (DFS) |
Measure: | Pharmacokinetic profile of S64315 administered in combination with Azacitidine in plasma: Area Under the Curve (AUC) (Phase I - dose escalation) |
Time Frame: | At Day -13, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 7 and Cycle 1 Day 9 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic profile of S64315 administered in combination with Azacitidine in plasma: maximum Concentration (Cmax) (Phase I - dose escalation) |
Time Frame: | At Day -13, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 5, Cycle 1 Day 7 and Cycle 1 Day 9 (each cycle is 28 days) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Institut de Recherches Internationales Servier |
Trial Keywords
- Acute Myeloid Leukaemia
- Oncology
- Mcl-1 inhibitor
- Azacitidine
- Combination
- Phase I/II
- International
- Safety
- Maximum tolerated dose
Last Updated
June 28, 2021