Description:
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).
Title
- Brief Title: 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: 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
Clinical Trial IDs
- ORG STUDY ID:
CL1-65487-002
- SECONDARY ID:
2018-004170-97
- NCT ID:
NCT03755154
Conditions
- Relapse or Refractory Acute Myeloid Leukemia
- Relapse or Refractory Non-Hodgkin Lymphoma
- Relapse or Refractory Multiple Myeloma
- Relapse or Refractory Chronic Lymphocytic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
S65487- initial scheme | | S65487 - initial scheme |
S65487 - alternative scheme | | S65487 - alternative scheme |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
S65487 - initial scheme | Experimental | | |
S65487 - alternative scheme | Experimental | | - S65487 - alternative scheme
|
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) 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of Dose Limiting Toxicity (DLT) |
Time Frame: | until the end of the first cycle (each cycle is 21days) |
Safety Issue: | |
Description: | Safety criterion |
Secondary Outcome Measures
Measure: | The pharmacokinetic (PK) profile of S65487: Area Under the Curve (AUC) |
Time Frame: | Ramp up period (before C1D1), Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) |
Safety Issue: | |
Description: | |
Measure: | PK profile of S65487: Volume of distribution at steady-state (Vss) |
Time Frame: | Ramp up period (before C1D1), Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) |
Safety Issue: | |
Description: | |
Measure: | PK profile of S65487: total CLearance (CL) |
Time Frame: | Ramp up period (before C1D1), Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) |
Safety Issue: | |
Description: | |
Measure: | PK profile of S65487: terminal half-life (t½z) |
Time Frame: | Ramp up period (before C1D1), Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 (one cycle is 21 days) |
Safety Issue: | |
Description: | |
Measure: | Best Overall Response (BOR) |
Time Frame: | Through study completion, an average of 6 months |
Safety Issue: | |
Description: | Best Response observed during the treatment period |
Measure: | Overall Response Rate (ORR) |
Time Frame: | Through study completion, an average of 6 months |
Safety Issue: | |
Description: | Proportion of patients in whom a complete response (CR) or a partial response (PR) |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Institut de Recherches Internationales Servier |
Trial Keywords
- Leukemia
- Lymphoma
- Myeloma
- Dose-escalation
Last Updated
February 16, 2021