A Phase I/Ib Open-label, Multi-center Dose Escalation Study of JBH492 in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL)
Overview
- Phase
- Phase 1
- Intervention
- JBH492
- Conditions
- Non-Hodgkins Lymphoma
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Number of patients with dose reductions
- Status
- Terminated
- Last Updated
- 6 months ago
Overview
Brief Summary
The purpose of the First-In-Human study was to assess the safety, tolerability, pharmacokinetics (PK), immunogenicity and preliminary efficacy of JBH492 as single agent.
Detailed Description
This was a FIH, open-label, phase I/Ib, multi-center study, which consisted of a dose escalation part of JBH492 as a single agent, followed by an expansion part. The escalation part was conducted in patients with relapsed/refractory chronic lymphocytic leukemia (r/r CLL) and Non-Hodgkin's Lymphoma (r/r NHL). Once the maximum tolerated dose/recommended dose (MTD/RD) of single agent JBH492 was determined, the study continued with an expansion part with single agent JBH492 in defined patient populations.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For patients with CLL:
- •Confirmed diagnosis of chronic lymphocytic leukemia (CLL)
- •For patients with NHL:
- •Histologically confirmed diagnosis of B- or T-cell non-Hodgkins lymphoma (NHL).
- •Must have a site of disease amenable to biopsy, and be suitable and willing to undergo study required biopsies at screening and during therapy.
- •Exclusion Criteria, applicable to both CLL and NHL:
- •History of anaphylactic or other severe hypersensitivity/infusion reactions to ADCs, monoclonal antibodies (mAbs) and/or their excipients such that the patient in unable to tolerate immunoglobulin/monoclonal antibody administration
- •Any prior history of treatment with maytansine (DM1 or DM4)-based ADC
- •Known intolerance to a maytansinoid
- •Patients with any active or chronic corneal disorders
Exclusion Criteria
- Not provided
Arms & Interventions
JBH492 single agent
Patients with R/R CLL or NHL
Intervention: JBH492
Outcomes
Primary Outcomes
Number of patients with dose reductions
Time Frame: 32 months
Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions
Incidence and severity of dose limiting toxicities (DLTs)
Time Frame: 32 months
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value that occurs during the first cycle of treatment with JBH492 and meets any of the protocol specified criteria, unless incontrovertibly related to underlying disease, intercurrent illness or concomitant medications.
Incidence and severity of Serious Adverse Events (SAEs)
Time Frame: 32 months
A Serious adverse event (SAE) is defined as one of the following: * Is fatal or life-threatening * Results in persistent or significant disability/incapacity * Constitutes a congenital anomaly/birth defect * Is medically significant * Requires inpatient hospitalization or prolongation of existing hospitalization.
Incidence and severity of Adverse Events (AEs)
Time Frame: 32 months
An adverse event ( treatment emergent) is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
Number of patients with dose interruptions
Time Frame: 32 months
Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
Dose intensity
Time Frame: 32 months
Tolerability measured by the dose intensity of study drug, Relative Dose intensity for subjects with non-zero duration of exposure is computed as the ratio of dose intensity and planned dose intensity
Secondary Outcomes
- PK parameter T1/2(32 months)
- Best overall response (BOR)(32 months)
- Pharmacokinetics (PK) parameter AUClast(32 months)
- PK parameter AUCtau(32 months)
- PK parameter Tmax(32 months)
- Progression Free Survival (PFS)(32 months)
- PK parameter AUCinf(32 months)
- PK parameter Cmax and Cmin(32 months)
- Overall response rate (ORR)(32 months)
- Duration of Response (DOR)(32 months)
- Incidence of anti-JBH492 antibodies(32 months)