Acute Myeloid LeukaemiaPhase 1NCT03672695

Phase I Dose Escalation Study of Intravenously Administered S64315 in Combination With Orally Administered Venetoclax in Patients With Acute Myeloid Leukaemia.

A Phase 1 study testing S 64315 (also referred as MIK665) and venetoclax in people with Acute Myeloid Leukaemia, run by Institut de Recherches Internationales Servier at 7 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine the safety profile, tolerability and the Recommended Phase 2 Dose of the combination S64315 with venetoclax in patients with Acute Myeloid Leukaemia. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Myeloid Leukaemia
What is being tested?: S 64315 (also referred as MIK665) and venetoclax
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 7 sitesin 3 countries
Study dates: 28 Nov 2018to 30 May 2023
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female aged ≥ 18 years;
Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization (WHO) 2016 classification (Arber, 2016), 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 and without established alternative therapy or
≥ 65 years not previously treated for AML and who are not candidates for intensive chemotherapy nor candidates for established alternative therapy
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

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Able to comply with study procedures
Adequate renal function within 7 days before the inclusion of the patient defined as:
Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance (determined by MDRD) > 50 mL/min/1.73m2
Adequate hepatic function within 7 days before the inclusion of the patient defined as:
AST and ALT ≤ 1.5 x ULN
Total serum bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's syndrome, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN

Who cannot join

Participant already enrolled and treated in the study
Pregnancy, breastfeeding or possibility of becoming pregnant during the study
Participation in another interventional study requiring investigational treatment intake at the same time or within 2 weeks or at least 5 halflives (whichever is longer) prior to first dose of IMP (participation in non-interventional registries or epidemiological studies is allowed). In case of biologic agents with a long half life such as CART cells, immune checkpoint antibodies, bispecific antibodies a flat wash-out of 28 days will be acceptable
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 (NCICTCAE, version 4.03).
Known carriers of HIV antibodies
Known history of significant liver disease

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Uncontrolled hepatitis B or C infection
Known active acute or chronic pancreatitis
History of myocardial infarction (MI), unstable angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment
Any factors that could increase the risk of QTc prolongation or risk of arrhythmic events.

Trial locations and contacts

7 sites in 3 countries.

Country

City, postcode or hospital

7 sites in 3 countries

France3 sites

Institut Paoli-Calmettes
Marseille
Hopital Saint-Antoine
Paris
Institut Universitaire du Cancer Toulouse - Oncopole
Toulouse

Other trials in France

United States2 sites

The University of Texas MD Anderson Cancer Center, Houston, TX
Houston, Texas, 77030
Smilow Cancer Hospital at Yale
New Haven, Connecticut, 06511

Other trials in United States

Australia2 sites

Peter MacCallum cancer centrer
Melbourne
The Alfred Hospital Department of Haematology
Victoria Park

Other trials in Australia

About this study

Official title: An International Phase Ib Multicentre Study to Characterize the Safety and Tolerability of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Orally Administered Venetoclax, a Selective Bcl-2 Inhibitor in Patients With Acute Myeloid Leukaemia (AML).

The purpose of this study is to determine the safety profile, tolerability and the Recommended Phase 2 Dose of the combination S64315 with venetoclax in patients with Acute Myeloid Leukaemia.

Conditions: Acute Myeloid Leukaemia
Being tested: S 64315 (also referred as MIK665) and venetoclax
Medical subject headings: Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

S 64315 (also referred as MIK665) and venetoclaxCombination product
The treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.
S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored.
Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.

Study groups in NCT03672695
Study group	Role	What they receive
Initial Schedule - S64315 low dose and venetoclax high dose administered in combination	Experimental	Not described Receives: Combination Product: S 64315 (also referred as MIK665) and venetoclax
Initial Schedule - S64315 medium dose and venetoclax low dose administered in combination	Experimental	Not described Receives: Combination Product: S 64315 (also referred as MIK665) and venetoclax
Initial Schedule - S64315 medium dose and venetoclax medium dose administered in combination	Experimental	Not described Receives: Combination Product: S 64315 (also referred as MIK665) and venetoclax
Initial Schedule - S64315 medium dose and venetoclax high dose administered in combination	Experimental	Not described Receives: Combination Product: S 64315 (also referred as MIK665) and venetoclax
Initial Schedule - S64315 high dose and venetoclax medium dose administered in combination	Experimental	Not described Receives: Combination Product: S 64315 (also referred as MIK665) and venetoclax
Alternative Schedule - Venetoclax medium dose administered with no S64315	Experimental	Not described Receives: Combination Product: S 64315 (also referred as MIK665) and venetoclax
Alternative Schedule - S64315 medium dose and venetoclax medium dose administered in combination	Experimental	Not described Receives: Combination Product: S 64315 (also referred as MIK665) and venetoclax
Alternative Schedule - S64315 high dose and venetoclax low dose administered in combination	Experimental	Not described Receives: Combination Product: S 64315 (also referred as MIK665) and venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of Dose Limiting Toxicity (DLTs)
Measured: At the end of cycle 1 (each cycle is 21 or 28 days).
Incidence and severity of AEs
Measured: Through study completion, an average of 6 months.
Incidence and severity of SAEs
Measured: Through study completion, an average of 6 months.
Number of participants with dose interruptions "will be measured and reported in the Outcome Measure results data table.
Measured: Through study completion, an average of 6 months.
Number of participants with dose reductions "will be measured and reported in the Outcome Measure results data table.
Measured: Through study completion, an average of 6 months.
Dose intensity
Measured: Through study completion, an average of 6 months.

Secondary outcomes (4)

Anti-leukemic activity
Using blood, bone marrow aspirate and medullary biopsy if available according to ELN 2017 criteria
Measured: Through study completion, an average of 6 months.
Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Area Under the Curve (AUC)
Measured: From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).
Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Concentration at the end of infusion (Cinf)
Measured: From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).
Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: terminal half-life (t½z)
Measured: From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Nov 201830 May 2023

First posted14 Sep 2018
Study start28 Nov 2018
Primary completion12 Nov 2022
Study completion30 May 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Acute Myeloid LeukaemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03672695
Sponsor's protocol ID: CL1-64315-002
Other IDs: 2018-001809-88, 2018
Status last verified: Feb 2024
First submitted: 4 Sep 2018
Last updated: 5 Feb 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

All Acute Myeloid Leukaemia trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An International Phase Ib Multicentre Study to Characterize the Safety and Tolerability of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Orally Administered Venetoclax, a Selective Bcl-2 Inhibitor in Patients With Acute Myeloid Leukaemia (AML).
ClinicalTrials.gov ID: NCT03672695
Acronym / sponsor ID: CL1-64315-002
Conditions: Acute Myeloid Leukaemia
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: Institut de Recherches Internationales ServierUniversity, hospital or other
Collaborators: ADIR, a Servier Group company
Study start: 28 Nov 2018 (actual)
Primary completion: 12 Nov 2022 (actual)
Study completion: 30 May 2023 (actual)
First posted: 14 Sep 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to determine the safety profile, tolerability and the Recommended Phase 2 Dose of the combination S64315 with venetoclax in patients with Acute Myeloid Leukaemia.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 8

Arm	Type	Receives
Initial Schedule - S64315 low dose and venetoclax high dose administered in combination	Experimental	Combination Product: S 64315 (also referred as MIK665) and venetoclax
Initial Schedule - S64315 medium dose and venetoclax low dose administered in combination	Experimental	Combination Product: S 64315 (also referred as MIK665) and venetoclax
Initial Schedule - S64315 medium dose and venetoclax medium dose administered in combination	Experimental	Combination Product: S 64315 (also referred as MIK665) and venetoclax
Initial Schedule - S64315 medium dose and venetoclax high dose administered in combination	Experimental	Combination Product: S 64315 (also referred as MIK665) and venetoclax
Initial Schedule - S64315 high dose and venetoclax medium dose administered in combination	Experimental	Combination Product: S 64315 (also referred as MIK665) and venetoclax
Alternative Schedule - Venetoclax medium dose administered with no S64315	Experimental	Combination Product: S 64315 (also referred as MIK665) and venetoclax
Alternative Schedule - S64315 medium dose and venetoclax medium dose administered in combination	Experimental	Combination Product: S 64315 (also referred as MIK665) and venetoclax
Alternative Schedule - S64315 high dose and venetoclax low dose administered in combination	Experimental	Combination Product: S 64315 (also referred as MIK665) and venetoclax

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Male or female aged ≥ 18 years;
Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization (WHO) 2016 classification (Arber, 2016), excluding acute promyelocytic leukaemia (APL, French-American British M3 classification):
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Able to comply with study procedures
Adequate renal function within 7 days before the inclusion of the patient defined as:

Key exclusion criteria (10 listed)

Participant already enrolled and treated in the study
Pregnancy, breastfeeding or possibility of becoming pregnant during the study
Participation in another interventional study requiring investigational treatment intake at the same time or within 2 weeks or at least 5 halflives (whichever is longer) prior to first dose of IMP (participation in non-interventional registries or epidemiological studies is allowed). In case of biologic agents with a long half life such as CART cells, immune checkpoint antibodies, bispecific antibodies a flat wash-out of 28 days will be acceptable
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 (NCICTCAE, version 4.03).
Known carriers of HIV antibodies

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
S 64315 (also referred as MIK665) and venetoclaxThe treatment combination period can only begin after the planned dose of venetoclax is reached. Depending on the administration dosing schedule, the combination treatment at the planned doses may be preceded by a 2-week Lead-In Dose period of S64315 (fixed dose) during which the patient continues to receive venetoclax daily. Once the planned dose of both drugs is reached the schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax. S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 250 mg once a week might be explored. Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.	Combination product	Alternative Schedule - S64315 high dose and venetoclax low dose administered in combination, Alternative Schedule - S64315 medium dose and venetoclax medium dose administered in combination, Alternative Schedule - Venetoclax medium dose administered with no S64315, Initial Schedule - S64315 high dose and venetoclax medium dose administered in combination, Initial Schedule - S64315 low dose and venetoclax high dose administered in combination, Initial Schedule - S64315 medium dose and venetoclax high dose administered in combination, Initial Schedule - S64315 medium dose and venetoclax low dose administered in combination, Initial Schedule - S64315 medium dose and venetoclax medium dose administered in combination

Primary outcome

Incidence of Dose Limiting Toxicity (DLTs)
Time frame: At the end of cycle 1 (each cycle is 21 or 28 days).
Incidence and severity of AEs
Time frame: Through study completion, an average of 6 months.
Incidence and severity of SAEs
Time frame: Through study completion, an average of 6 months.
Number of participants with dose interruptions "will be measured and reported in the Outcome Measure results data table.
Time frame: Through study completion, an average of 6 months.
Number of participants with dose reductions "will be measured and reported in the Outcome Measure results data table.
Time frame: Through study completion, an average of 6 months.
Dose intensity
Time frame: Through study completion, an average of 6 months.

4 secondary outcomes

Anti-leukemic activity
Time frame: Through study completion, an average of 6 months.
Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Area Under the Curve (AUC)
Time frame: From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).
Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Concentration at the end of infusion (Cinf)
Time frame: From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).
Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: terminal half-life (t½z)
Time frame: From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days).

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2024.
Find Results on Servier Clinical Trial Data websiteLink provided by the sponsor.
Link to Lay Summary and Results SummaryLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Related trials for Acute Myeloid Leukaemia

RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Andrew WEI principal investigator

The Alfred Hospital, Melbourne, Victoria

7 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing S 64315 (also referred as MIK665) and venetoclax in people with Acute Myeloid Leukaemia, run by Institut de Recherches Internationales Servier at 7 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in France, United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose Limiting Toxicity (DLTs) (time frame: At the end of cycle 1 (each cycle is 21 or 28 days).). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03672695.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2024.