Clinical trial NCT02992483: Phase I Study of MIK665, a Mcl-1 Inhibitor, in Patients With Refractory or Relapsed Lymphoma or Multiple Myeloma
Official title: Phase I Open Label, Multi-center Study to Characterize the Safety, Tolerability and Pharmacokinetics of Intravenously Administered MIK665, a Mcl-1 Inhibitor, in Patients With Refractory or Relapsed Lymphoma or Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma (MM), Lymphoma, Large B-Cell, Diffuse (DLBCL), Lymphoma
Keywords: multiple myeloma
lymphoma
dlbcl
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-12-14
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this first in human study is to assess safety, tolerability, PK and preliminary clinical activity and to estimate the MTD(s)/RDE(s) of MIK665 (also referred as S64315) as single agent administered intravenously (i.v.) in adult patients with refractory or relapsed lymphoma or multiple myeloma.

Detailed description: The design of this phase I, open label, dose finding study was chosen in order to characterize the safety and tolerability of MIK665 and to determine the Maximal Tolerated Dose(s) (MTD(s)) and/or Recommended Dose(s) for Expansion (RDE(s)).

This study will utilize a Bayesian Hierarchical model to guide dose escalation and estimate the MTD(s) based on the dose-DLT relationship(s) for MIK665 in the indications.

The expansion part of the study will employ an open-label multiple arm design. The purpose of the expansion part is to further assess safety, tolerability, PK, PD and the anti-tumor activity of MIK665 at the selected RDE/s for Multiple Myeloma (MM) and MYC positive Diffuse large B-Cell Lymphoma (DLBCL) identified in the dose-escalation part.

Eligibility criteria: Inclusion Criteria

* Age ≥ 18 years.
* Histologically confirmed lymphoma (WHO classification), or confirmed MM (IMWG), that is relapsed and/or refractory.
* Other Inclusion Criteria May Apply.

Exclusion Criteria

* Known history of chronic liver disease
* History of chronic pancreatitis.
* Prior treatment with Mcl-1 inhibitor.
* Other Exclusion Criteria May Apply.

Primary outcomes:
measure: Incidence and severity of AEs and SAEs, incl. changes in laboratory parameters, vital signs and ECGs.
timeFrame: 2 years
measure: Incidence of DLTs during the first cycle of treatment with single agent MIK665 during the dose escalation phase only
timeFrame: 2 years
measure: Tolerability: Dose interruptions
timeFrame: 2 years
measure: Tolerability: Dose reductions
timeFrame: 2 years
measure: Tolerability: Dose intensity
timeFrame: 2 years
Secondary outcomes:
measure: Best Overall response (BOR) per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma
timeFrame: 2 years
measure: Area Under Curve (AUC)
timeFrame: 2 years
measure: Maximum Plasma Concentration (Cmax)
timeFrame: 2 years
measure: Terminal elimination half-life (T1/2)
timeFrame: 2 years
measure: Apparent volume of distribution (Vz)
timeFrame: 2 years
measure: Clearance (CL)
timeFrame: 2 years
measure: Duration of Response (DOR)per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma
timeFrame: 2 years
measure: Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) criteria for Myeloma; and per revised criteria for staging of the International Working Group (IWG) guidelines for Lymphoma
timeFrame: 2 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center/University of Texas MD Anderson CC
state: Texas
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
Study officials:
References: