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

Relapsed or Refractory Multiple Myeloma Clinical Trial

Official title:

Phase I, Open Label, Non-randomised, Non-comparative, Multi-center Study, Evaluating S65487, a Bcl-2 Inhibitor Intravenously Administered, in Patients With Relapsed or Refractory Acute Myeloid Leukemia, Non Hodgkin Lymphoma, Multiple Myeloma or Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03755154
• Other study ID #: CL1-65487-002
• Secondary ID: 2018-004170-97
• Status: Completed
• Phase: Phase 1
• Start date: July 17, 2019
• Est. completion date: November 6, 2023

Study information

• Verified date: March 2024
• Source: Servier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 6, 2023
• Est. primary completion date: November 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Acute Myeloid Leukemia
• Relapsed or Refractory Chronic Lymphocytic Leukemia
• Relapsed or Refractory Multiple Myeloma

Intervention

Drug:
• S65487- initial scheme
S65487 is administered as single agent via i.v. infusion once a week on a 3-week cycle.
• 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.

Locations

Country	Name	City	State
Australia	The Alfred Hospital Malignant Haematology & Stem Cell Transplantation Services	Melbourne	Victoria
France	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
Spain	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
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	The Christie NHS foundation Trust	Manchester
United Kingdom	Freeman Hospital	Newcastle

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier	ADIR, a Servier Group company

Countries where clinical trial is conducted

Australia,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicity (DLT)	Safety criterion	until the end of the first cycle (each cycle is 21days)
Primary	Incidence and severity of Adverse Events	Safety and tolerability criteria	through study completion an average of 6 months
Primary	Incidence and severity of Serious Adverse Events	Safety and tolerability criteria	through study completion an average of 6 months
Primary	Number of participants with dose reductions		through study completion an average of 6 months
Primary	Number of participants with dose interruptions		through study completion an average of 6 months
Primary	Dose intensity		through study completion an average of 6 months
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Best Overall Response (BOR)	Best Response observed during the treatment period	Through study completion, an average of 6 months
Secondary	Overall Response Rate (ORR)	Proportion of patients in whom a complete response (CR) or a partial response (PR)	Through study completion, an average of 6 months

External Links

•   Find Results on Servier Clinical Trial Data website