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

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ClinicalTrials.gov Identifier: NCT03755154
Recruitment Status : Recruiting
First Posted : November 27, 2018
Last Update Posted : August 2, 2019
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

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).

Condition or disease Intervention/treatment Phase
Relapse or Refractory Acute Myeloid Leukemia Relapse or Refractory Non-Hodgkin Lymphoma Relapse or Refractory Multiple Myeloma Drug: S65487 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 17, 2019
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023


Arm Intervention/treatment
Experimental: S65487 Drug: S65487
S65487 is administered as single agent via i.v. infusion on a 3-week cycle.




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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • 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.

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): NCT03755154


Contacts
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Contact: Institut de Recherches Internationales Servier Clinical Studies Department +33 1 55 72 43 66 clinicaltrials@servier.com

Locations
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Australia, Victoria
The Alfred Recruiting
Melbourne, Victoria, Australia, 3004
France
CENTRE HOSPITALIER UNIVERSITAIRE DE LILLE Hôpital HURIEZ Recruiting
Lille, France, 59037
CHU Nantes Hôtel Dieu Recruiting
Nantes, France, 44093
Spain
Clinica Universidad de Navarra Recruiting
Madrid, Spain, 28027
Clínica Universidad Navarra- Servicio de Hematología Recruiting
Pamplona, Spain, 31008
Hospital Clínico Universitario de Salamanca- Servicio de Hematología (4a planta) Recruiting
Salamanca, Spain, 37007
Hospital Universitario La Fe - Servicio de Hematología - Torre F - Planta 7 Recruiting
Valencia, Spain, 46026
United Kingdom
Clatterbridge Hospital Not yet recruiting
Bebington, United Kingdom, L63 4JY
The Christie NHS foundation Trust Not yet recruiting
Manchester, United Kingdom, M20 4BX
Freeman Hospital Recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Institut de Recherches Internationales Servier
ADIR, a Servier Group company

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

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Responsible Party: Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier: NCT03755154     History of Changes
Other Study ID Numbers: CL1-65487-002
2018-004170-97 ( EudraCT Number )
First Posted: November 27, 2018    Key Record Dates
Last Update Posted: August 2, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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 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 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: https://clinicaltrials.servier.com/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Servier ( Institut de Recherches Internationales Servier ):
Leukemia
Lymphoma
Myeloma
Dose-escalation
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Myeloid, Acute
Lymphoma, Non-Hodgkin
Recurrence
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Disease Attributes
Pathologic Processes