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

NCT03755154 | Terminated Phase 1

• 2 other identifiers: CL1-65487-0022018-004170-97
• Study Type: interventional
• Target: 60
• Locations: 4 countries
• Sites: 11

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).

Conditions

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

Keywords

Leukemia; Lymphoma; Myeloma; Dose-escalation

Outcome Measures

Primary Outcomes (6)

• Incidence of Dose Limiting Toxicity (DLT)

  Safety criterion

  until the end of the first cycle (each cycle is 21days)

• Incidence and severity of Adverse Events

  Safety and tolerability criteria

  through study completion an average of 6 months

• Incidence and severity of Serious Adverse Events

  Safety and tolerability criteria

  through study completion an average of 6 months

• Number of participants with dose reductions

  through study completion an average of 6 months

• Number of participants with dose interruptions

  through study completion an average of 6 months

• Dose intensity

  through study completion an average of 6 months

Secondary Outcomes (6)

• The pharmacokinetic (PK) profile of S65487: Area Under the Curve (AUC)

  Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)

• PK profile of S65487: Volume of distribution at steady-state (Vss)

  Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)

• PK profile of S65487: total CLearance (CL)

  Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)

• PK profile of S65487: terminal half-life (t½z)

  Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3 (alternative schedule only), Cyle 1 Day 5 (alternative schedule only), Cycle 1 Day 8, Cycle 1 Day 9, Day 1 of next cycles (one cycle is 21 days)

• Best Overall Response (BOR)

  Through study completion, an average of 6 months

Study Arms (2)

S65487 - initial scheme

EXPERIMENTAL

Drug: S65487- initial scheme

S65487 - alternative scheme

EXPERIMENTAL

Drug: S65487 - alternative scheme

Interventions

S65487- initial scheme DRUG

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

S65487 - initial scheme

S65487 - alternative scheme 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.

S65487 - alternative scheme

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead
• ADIR, a Servier Group company: collaborator

Study Sites (11)

The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services

Melbourne, Victoria, 3004, Australia

Location

Centre Hospitalier Universitaire Régionale de Lille Hôpital Huriez

Lille, 59037, France

Location

CHU Nantes Hôtel Dieu

Nantes, 44093, France

Location

CHU de Nice - Hôpital l'Archet 1 Hématologie clinique

Nice, 06200, France

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Clínica Universidad Navarra- Servicio de Hematología

Pamplona, 31008, Spain

Location

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

Salamanca, 37007, Spain

Location

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

Valencia, 46026, Spain

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

The Christie NHS foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Freeman Hospital

Newcastle, NE7 7DN, United Kingdom

Location

Related Links

• Find Results on Servier Clinical Trial Data website

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia; Lymphoma; Neoplasms, Plasma Cell

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Chronic Disease

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 27, 2018
• Study Start: July 17, 2019
• Primary Completion: November 6, 2023
• Study Completion: November 6, 2023
• Last Updated: October 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

FR (3); ES (4); AU (1); GB (3)