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History of Changes for Study: NCT03755154
Study of a New Intravenous Drug, Called S65487, in Patients With Acute Myeloid Leukemia, Non Hodgkin Lymphoma or Multiple Myeloma
Latest version (submitted December 5, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 November 26, 2018 None (earliest Version on record)
2 May 17, 2019 Study Status, References, Contacts/Locations and Oversight
3 August 1, 2019 Recruitment Status, Study Status and Contacts/Locations
4 January 31, 2020 Contacts/Locations, Study Status, IPDSharing, Eligibility and Study Description
5 September 25, 2020 Study Status and IPDSharing
6 September 30, 2020 Study Identification, Eligibility, Conditions, Study Description and Study Status
7 November 4, 2020 Study Status and Contacts/Locations
8 February 4, 2021 Arms and Interventions, Study Design, Study Status and Outcome Measures
9 February 12, 2021 Study Design and Study Status
10 March 11, 2022 Contacts/Locations, Study Status, Eligibility, Outcome Measures, Arms and Interventions, Conditions and Study Identification
11 April 13, 2022 Study Status and Contacts/Locations
12 December 5, 2022 Study Status and Study Design
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Study NCT03755154
Submitted Date:  November 26, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: CL1-65487-002
Brief Title: Study of a New Intravenous Drug, Called S65487, in Patients With Acute Myeloid Leukemia, Non Hodgkin Lymphoma or Multiple Myeloma
Official Title: Phase I, Open Label, Non-randomised, Non-comparative, Multi-center Study, Evaluating S65487, a Bcl-2 Inhibitor Intravenously Administered, in Patients With Relapse or Refractory Acute Myeloid Leukemia, Non Hodgkin Lymphoma or Multiple Myeloma
Secondary IDs: 2018-004170-97 [EudraCT Number]
Open or close this module Study Status
Record Verification: November 2018
Overall Status: Not yet recruiting
Study Start: March 2019
Primary Completion: May 2023 [Anticipated]
Study Completion: May 2023 [Anticipated]
First Submitted: November 13, 2018
First Submitted that
Met QC Criteria:
November 26, 2018
First Posted: November 27, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
November 26, 2018
Last Update Posted: November 27, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Institut de Recherches Internationales Servier
Responsible Party: Sponsor
Collaborators: ADIR, a Servier Group company
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: The purpose of this first in human study is to assess safety, tolerability, Pharmacokinetic (PK) and preliminary clinical activity and to estimate the Maximum Tolerated Doses (MTD(s))/ Recommended Phase 2 Doses (RP2D(s)) of S65487 as single agent administered intravenously (i.v.) in adult patients with refractory or relapsed Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL) or Multiple Myeloma (MM).
Detailed Description:

This study is designed in two parts: one part for dose escalation, one part for dose expansion.The dose escalation part will be followed by expansion part at the MTD(s)/RP2D(s)

This study will utilize a Bayesian Hierarchical model to guide dose escalation and estimate the MTD(s) based on the Dose Limiting Toxicity (DLT) relationship(s) for S65487 in the indications.

Open or close this module Conditions
Conditions: Relapse or Refractory Acute Myeloid Leukemia
Relapse or Refractory Non-Hodgkin Lymphoma
Relapse or Refractory Multiple Myeloma
Keywords: Leukemia
Lymphoma
Myeloma
Dose-escalation
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 60 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: S65487 Drug: S65487
S65487 is administered as single agent via i.v. infusion on a 3-week cycle.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Incidence of Dose Limiting Toxicity (DLT)
[ Time Frame: until the end of the first cycle (each cycle is 21days) ]

Safety criterion
2. Incidence and severity of Adverse Events
[ Time Frame: through study completion an average of 6 months ]

Safety and tolerability criteria
3. Incidence and severity of Serious Adverse Events
[ Time Frame: through study completion an average of 6 months ]

Safety and tolerability criteria
4. Number of participants with dose reductions
[ Time Frame: through study completion an average of 6 months ]

5. Number of participants with dose interruptions
[ 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. The pharmacokinetic (PK) profile of S65487: Area Under the Curve (AUC)
[ Time Frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) ]

2. PK profile of S65487: Volume of distribution at steady-state (Vss)
[ Time Frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) ]

3. PK profile of S65487: total CLearance (CL)
[ Time Frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) ]

4. PK profile of S65487: terminal half-life (t½z)
[ Time Frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) ]

5. Best Overall Response (BOR)
[ Time Frame: Through study completion, an average of 6 months ]

Best Response observed during the treatment period
6. Overall Response Rate (ORR)
[ Time Frame: Through study completion, an average of 6 months ]

Proportion of patients in whom a complete response (CR) or a partial response (PR)
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML, excluding acute promyelocytic leukaemia with relapsed or refractory disease without established alternative therapy. Or patients with measurable confirmed Multiple Myeloma (IMWG) with relapsed or refractory disease who have previously received at least three lines of treatment and without established alternative therapy. Or patients with histologically and measurable confirmed Non Hodgkin Lymphoma defined as Diffuse Large B cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) with relapsed or refractory disease who have received at least two lines of therapy (including rituximab) and without established alternative therapy.
  • ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2.
  • For NHL and MM patients: haematological function (independent of any growth factor support) based on the last assessment performed before inclusion, defined as: absolute neutrophil count (ANC) ≥ 1 x 109/L, haemoglobin ≥ 8 g/dL, platelet count ≥ 50 x 109/L.
  • For AML patients: circulating Blood White Cell count (WBC count) < 25 x 109/L (with or without use of hydroxycarbamide) based on the last assessment performed before inclusion.
  • Adequate renal function based on the last assessment performed before inclusion, assessed as Glomerular Filtration Rate (GFR) using Modification of Diet in Renal Disease (MDRD) Formula.
  • Adequate hepatic function based on the last assessment performed before inclusion.

Exclusion Criteria:

  • Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
  • Participation in another interventional study at the same time or another interventional study requiring investigational treatment intake within 3 weeks or at least 5 half-lives (whichever is longer) prior to the first S65487 administration.
  • Participant already enrolled in the study (informed consent signed) and has received at least one dose of S65487.
  • Patients who have not recovered from toxicity of previous anticancer therapy, including grade ≥ 2 non-hematologic toxicity, prior to the first IMP administration (including peripheral neurotoxicity). Certain toxicities will not be considered in this category (e.g. alopecia).
  • Patients refractory to a previous treatment with a Bcl-2 inhibitor.
  • For AML patients : Allogenic stem cell transplant within 3 months before the first IMP administration and/or patients who still receive immunosuppressive treatment and/or patients with active Graft-versus-host disease.
  • For NHL and MM patients Prior allogenic stem cell transplant before the first IMP administration and/or Autologous stem cell transplant within 3 months before the first IMP administration.
Open or close this module Contacts/Locations
Central Contact Person: Institut de Recherches Internationales Servier Clinical Studies Department
Telephone: +33 1 55 72 43 66
Email: clinicaltrials@servier.com
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes

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

They can ask for 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 Information:
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: https://clinicaltrials.servier.com/
Open or close this module References
Citations:
Links:
Available IPD/Information: Type: Individual Participant Data Set
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Type: Study-level clinical trial data
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