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Study of a New Intravenous Drug, Called S65487, in Patients With Acute Myeloid Leukemia, Non Hodgkin Lymphoma, Multiple Myeloma or Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03755154
Recruitment Status : Recruiting
First Posted : November 27, 2018
Last Update Posted : October 5, 2020
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

Tracking Information
First Submitted Date  ICMJE November 13, 2018
First Posted Date  ICMJE November 27, 2018
Last Update Posted Date October 5, 2020
Actual Study Start Date  ICMJE July 17, 2019
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
  • Incidence of Dose Limiting Toxicity (DLT) [ Time Frame: until the end of the first cycle (each cycle is 21days) ]
    Safety criterion
  • Incidence and severity of Adverse Events [ Time Frame: through study completion an average of 6 months ]
    Safety and tolerability criteria
  • Incidence and severity of Serious Adverse Events [ Time Frame: through study completion an average of 6 months ]
    Safety and tolerability criteria
  • Number of participants with dose reductions [ Time Frame: through study completion an average of 6 months ]
  • Number of participants with dose interruptions [ Time Frame: through study completion an average of 6 months ]
  • Dose intensity [ Time Frame: through study completion an average of 6 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Best Overall Response (BOR) [ Time Frame: Through study completion, an average of 6 months ]
    Best Response observed during the treatment period
  • 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of a New Intravenous Drug, Called S65487, in Patients With Acute Myeloid Leukemia, Non Hodgkin Lymphoma, Multiple Myeloma or Chronic Lymphocytic Leukemia
Official Title  ICMJE 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, Multiple Myeloma or Chronic Lymphocytic Leukemia
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), Multiple Myeloma (MM) or Chronic Lymphocytic Leukemia (CLL).
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 an adaptative Bayesian Logistic Regression model to guide dose escalation and estimate the MTD(s) based on the Dose Limiting Toxicity (DLT) relationship(s) for S65487 in the indications.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapse or Refractory Acute Myeloid Leukemia
  • Relapse or Refractory Non-Hodgkin Lymphoma
  • Relapse or Refractory Multiple Myeloma
  • Relapse or Refractory Chronic Lymphocytic Leukemia
Intervention  ICMJE Drug: S65487
S65487 is administered as single agent via i.v. infusion on a 3-week cycle.
Study Arms  ICMJE Experimental: S65487
Intervention: Drug: S65487
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 26, 2018)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2023
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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), High-Grade B cell Lymphoma with relapsed or refractory disease who have received at least two lines of therapy (including rituximab) and without established alternative therapy. Or patients with Chronic Lymphocytic Leukemia (CLL) who have relapsed or are refractory (except treatment failure), as defined per iwCLL, from venetoclax treatment and without established alternative therapy.
  • ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2.
  • For NHL, MM patients and CLL 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 NHL and MM patients, platelet count ≥ 30 x 109/L for CLL patients.
  • 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 within 3 months before the first IMP administration and/or patients with active Graft-versus-host disease within 3 months before the first IMP administration and/or patient who receive donor lymphocyte infusion (DLI) within 3 months before the first IMP administration.
  • For NHL, MM and CLL 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Institut de Recherches Internationales Servier Clinical Studies Department +33 1 55 72 43 66 clinical.trial.management@servier.com
Listed Location Countries  ICMJE Australia,   France,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03755154
Other Study ID Numbers  ICMJE CL1-65487-002
2018-004170-97 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: 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/
Responsible Party Servier ( Institut de Recherches Internationales Servier )
Study Sponsor  ICMJE Institut de Recherches Internationales Servier
Collaborators  ICMJE ADIR, a Servier Group company
Investigators  ICMJE Not Provided
PRS Account Servier
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP