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

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ClinicalTrials.gov Identifier: NCT03672695
Recruitment Status : Recruiting
First Posted : September 14, 2018
Last Update Posted : April 16, 2019
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier

Brief 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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukaemia Combination Product: S 64315 (also referred as MIK665) and venetoclax Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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).
Actual Study Start Date : November 28, 2018
Estimated Primary Completion Date : March 31, 2022
Estimated Study Completion Date : March 31, 2022


Arm Intervention/treatment
Experimental: S64315 and venetoclax administered in combination Combination Product: S 64315 (also referred as MIK665) and venetoclax

The treatment combination period should start the day after the planned dose of venetoclax is reached. The initial 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 1000 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.





Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicity (DLTs) [ Time Frame: At the end of cycle 1 (each cycle is 21 or 28 days). ]
  2. Incidence and severity of AEs [ Time Frame: Through study completion, an average of 6 months. ]
  3. Incidence and severity of SAEs [ Time Frame: Through study completion, an average of 6 months. ]
  4. 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. ]
  5. 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. ]
  6. Dose intensity [ Time Frame: Through study completion, an average of 6 months. ]

Secondary Outcome Measures :
  1. Anti-leukemic activity [ Time Frame: Through study completion, an average of 6 months. ]
    Using blood, bone marrow aspirate and medullary biopsy if available according to ELN 2017 criteria

  2. 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). ]
  3. 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). ]
  4. 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). ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female aged ≥ 18 years;
  2. 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
  3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  4. Able to comply with study procedures
  5. 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

  6. Adequate hepatic function within 7 days before the inclusion of the patient defined as:

    • AST and ALT ≤ 3 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

Exclusion Criteria:

  1. Participant already enrolled and treated in the study
  2. Pregnancy, breastfeeding or possibility of becoming pregnant during the study
  3. 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
  4. 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).
  5. Known carriers of HIV antibodies
  6. Known history of significant liver disease
  7. Uncontrolled hepatitis B or C infection
  8. Known active acute or chronic pancreatitis
  9. History of myocardial infarction (MI), unstable angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03672695


Contacts
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Contact: Institut de Recherches Internationales Servier Clinical Studies Department +33155724366 clinicaltrials@servier.com

Locations
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United States, Connecticut
Smilow Cancer Hospital at Yale Not yet recruiting
New Haven, Connecticut, United States, 06511
United States, Texas
The University of Texas MD Anderson Cancer Center, Houston, TX Not yet recruiting
Houston, Texas, United States, 77030
Australia
Peter MacCallum cancer centrer Recruiting
Melbourne, Australia
The Alfred Hospital Department of Haematology Recruiting
Victoria Park, Australia
France
Institut Paoli-Calmettes Not yet recruiting
Marseille, France
Hopital Saint-Antoine Not yet recruiting
Paris, France
Institut Universitaire du Cancer Toulouse - Oncopole Not yet recruiting
Toulouse, France
Sponsors and Collaborators
Servier
ADIR, a Servier Group company
Investigators
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Principal Investigator: Andrew WEI The Alfred Hospital, Melbourne, Victoria

Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site

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Responsible Party: Servier
ClinicalTrials.gov Identifier: NCT03672695     History of Changes
Other Study ID Numbers: CL1-64315-002
2018-001809-88 ( EudraCT Number )
First Posted: September 14, 2018    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Plan Description: Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask all interventional clinical studies:

  • submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: http://clinicaltrials.servier.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Venetoclax
Antineoplastic Agents