Back to resultsSafety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL
Primary Purpose
Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
JBH492
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkins Lymphoma focused on measuring CLL, NHL, CCR7, JBH492, ADC, Chronic Lymphocytic Leukemia, Non-Hodgkins Lymphoma
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
- Patients who have any other condition that precludes monitoring of the retina or fundus
- Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated and provided that local treatment was completed >4 weeks before first dose of study treatment. Patients that have been effectively treated for CNS disease and are stable under systemic therapy may be enrolled provided all other inclusion and exclusion criteria are met. Patients who received prophylactic intrathecal treatment are eligible, if treatment discontinued >5 half-lives prior to the first dose of study treatment
- Impaired cardiac function or clinically significant cardiac disease
- Known history of Human Immunodeficiency Virus (HIV) infection
- Active HBV or HCV infection. Patients whose disease is controlled under antiviral therapy should not be excluded. Patients who are anti-HBcAb positive should be HBsAg negative and HBV-DNA negative to be eligible
Other inclusion and exclusion criteria may apply.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
JBH492 single agent
Arm Description
Patients with R/R CLL or NHL
Outcomes
Primary Outcome Measures
Incidence and severity of dose limiting toxicities (DLTs)
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 Adverse Events (AEs)
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.
Incidence and severity of Serious Adverse Events (SAEs)
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.
Number of patients with dose interruptions
Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
Number of patients with dose reductions
Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions
Dose intensity
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 Outcome Measures
Overall response rate (ORR)
The overall response rate (ORR), defined as the proportion of subjects with best overall response (BOR) of complete response (CR) or partial response (PR), as per local review and according to the iwCLL guideline (CLL) or Lugano Classification (NHL).
Best overall response (BOR)
The best overall response (BOR) is the best reponse recorded in a patient from the start of treatment until disease progression.
Duration of Response (DOR)
The time between the date of first documented response (CR or PR) and the date of first documented progression or death due to underlying cancer.
Progression Free Survival (PFS)
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause
Pharmacokinetics (PK) parameter AUClast
The area under the plasma concentration-time curve (AUC) of JBH492 from time zero to the last measurable concentration sampling time (tlast) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
PK parameter AUCinf
The AUC from time zero to infinity (mass × time × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
PK parameter AUCtau
The AUC calculated to the end of a dosing interval (tau) (mass × time × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
PK parameter Cmax and Cmin
The maximum (peak) and minimum observed serum drug concentration (mass × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
PK parameter Tmax
The time to reach maximum (peak) serum drug concentration (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
PK parameter T1/2
The elimination half-life associated with the terminal slope (λz) of a semi logarithmic concentration-time curve (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Incidence of anti-JBH492 antibodies
Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies)
Full Information
NCT ID
NCT04240704
First Posted
January 23, 2020
Last Updated
October 19, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04240704
Brief Title
Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 7, 2020 (Actual)
Primary Completion Date
March 21, 2024 (Anticipated)
Study Completion Date
March 21, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of the First-In-Human study is to assess safety, tolerability, pharmacokinetics (PK), immunogenicity and preliminary efficacy of JBH492 as single agent.
Detailed Description
This is a FIH, open-label, phase I/Ib, multi-center study, which consists of a dose escalation part of JBH492 as a single agent, followed by an expansion part. The escalation part will be conducted in patients with relapsed/refractory chronic lymphocytic leukemia (r/r CLL) and Non-Hodgkin's Lymphoma (r/r NHL). Once the MTD/RD of single agent JBH492 is determined, the study will continue with an expansion part with single agent JBH492 in defined patient populations
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia
Keywords
CLL, NHL, CCR7, JBH492, ADC, Chronic Lymphocytic Leukemia, Non-Hodgkins Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
JBH492 single agent
Arm Type
Experimental
Arm Description
Patients with R/R CLL or NHL
Intervention Type
Drug
Intervention Name(s)
JBH492
Intervention Description
Anti-CCR7 antibody-drug conjugate (ADC)
Primary Outcome Measure Information:
Title
Incidence and severity of dose limiting toxicities (DLTs)
Description
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.
Time Frame
32 months
Title
Incidence and severity of Adverse Events (AEs)
Description
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.
Time Frame
32 months
Title
Incidence and severity of Serious Adverse Events (SAEs)
Description
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.
Time Frame
32 months
Title
Number of patients with dose interruptions
Description
Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
Time Frame
32 months
Title
Number of patients with dose reductions
Description
Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions
Time Frame
32 months
Title
Dose intensity
Description
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
Time Frame
32 months
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
The overall response rate (ORR), defined as the proportion of subjects with best overall response (BOR) of complete response (CR) or partial response (PR), as per local review and according to the iwCLL guideline (CLL) or Lugano Classification (NHL).
Time Frame
32 months
Title
Best overall response (BOR)
Description
The best overall response (BOR) is the best reponse recorded in a patient from the start of treatment until disease progression.
Time Frame
32 months
Title
Duration of Response (DOR)
Description
The time between the date of first documented response (CR or PR) and the date of first documented progression or death due to underlying cancer.
Time Frame
32 months
Title
Progression Free Survival (PFS)
Description
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause
Time Frame
32 months
Title
Pharmacokinetics (PK) parameter AUClast
Description
The area under the plasma concentration-time curve (AUC) of JBH492 from time zero to the last measurable concentration sampling time (tlast) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Time Frame
32 months
Title
PK parameter AUCinf
Description
The AUC from time zero to infinity (mass × time × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Time Frame
32 months
Title
PK parameter AUCtau
Description
The AUC calculated to the end of a dosing interval (tau) (mass × time × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Time Frame
32 months
Title
PK parameter Cmax and Cmin
Description
The maximum (peak) and minimum observed serum drug concentration (mass × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Time Frame
32 months
Title
PK parameter Tmax
Description
The time to reach maximum (peak) serum drug concentration (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Time Frame
32 months
Title
PK parameter T1/2
Description
The elimination half-life associated with the terminal slope (λz) of a semi logarithmic concentration-time curve (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Time Frame
32 months
Title
Incidence of anti-JBH492 antibodies
Description
Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies)
Time Frame
32 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Patients who have any other condition that precludes monitoring of the retina or fundus
Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated and provided that local treatment was completed >4 weeks before first dose of study treatment. Patients that have been effectively treated for CNS disease and are stable under systemic therapy may be enrolled provided all other inclusion and exclusion criteria are met. Patients who received prophylactic intrathecal treatment are eligible, if treatment discontinued >5 half-lives prior to the first dose of study treatment
Impaired cardiac function or clinically significant cardiac disease
Known history of Human Immunodeficiency Virus (HIV) infection
Active HBV or HCV infection. Patients whose disease is controlled under antiviral therapy should not be excluded. Patients who are anti-HBcAb positive should be HBsAg negative and HBV-DNA negative to be eligible
Other inclusion and exclusion criteria may apply.
Facility Information:
Facility Name
Novartis Investigative Site
City
HUS
ZIP/Postal Code
FIN-00029
Country
Finland
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Novartis Investigative Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novartis Investigative Site
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Novartis Investigative Site
City
Chuo ku
State/Province
Tokyo
ZIP/Postal Code
104 0045
Country
Japan
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL
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