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

NCT ID: NCT03755154

Last Updated: 2024-10-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-17
• Study Completion Date: 2023-11-06

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.

Conditions

Relapsed or Refractory Acute Myeloid Leukemia; Relapsed or Refractory Non-Hodgkin Lymphoma; Relapsed or Refractory Multiple Myeloma; Relapsed or Refractory Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

S65487 - initial scheme

Group Type: EXPERIMENTAL

S65487- initial scheme

Intervention Type: DRUG

S65487 is administered as single agent via i.v. infusion once a week on a 3-week cycle.

S65487 - alternative scheme

Group Type: EXPERIMENTAL

S65487 - alternative scheme

Intervention Type: DRUG

S65487 is administered in 3 to 5 i.v. infusions the first week of each cycle then once a week on the rest of the 3-week cycle.

Interventions

S65487- initial scheme

S65487 is administered as single agent via i.v. infusion once a week on a 3-week cycle.

Intervention Type: DRUG

S65487 - alternative scheme

S65487 is administered in 3 to 5 i.v. infusions the first week of each cycle then once a week on the rest of the 3-week cycle.

Intervention Type: DRUG

Eligibility 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), 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/leukapheresis) 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADIR, a Servier Group company

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services

Melbourne, Victoria, Australia

Centre Hospitalier Universitaire Régionale de Lille Hôpital Huriez

Lille, , France

CHU Nantes Hôtel Dieu

Nantes, , France

CHU de Nice - Hôpital l'Archet 1 Hématologie clinique

Nice, , France

Clinica Universidad de Navarra

Madrid, , Spain

Clínica Universidad Navarra- Servicio de Hematología

Pamplona, , Spain

Hospital Clínico Universitario de Salamanca- Servicio de Hematología (4a planta)

Salamanca, , Spain

Hospital Universitario La Fe - Servicio de Hematología - Torre F - Planta 7

Valencia, , Spain

King's College Hospital NHS Foundation Trust

London, , United Kingdom

The Christie NHS foundation Trust

Manchester, , United Kingdom

Freeman Hospital

Newcastle, , United Kingdom

Countries

Australia; France; Spain; United Kingdom

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Clinical Study Report

View Document

Document Type: Study-level clinical trial data

View Document

Related Links

https://clinicaltrials.servier.com/

Find Results on Servier Clinical Trial Data website

Other Identifiers

2018-004170-97

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL1-65487-002

Identifier Type: -

Identifier Source: org_study_id