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Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04240704
Recruitment Status : Recruiting
First Posted : January 27, 2020
Last Update Posted : June 3, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE January 23, 2020
First Posted Date  ICMJE January 27, 2020
Last Update Posted Date June 3, 2022
Actual Study Start Date  ICMJE September 7, 2020
Estimated Primary Completion Date June 15, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2020)
  • 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 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.
  • 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.
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2020)
  • Overall response rate (ORR) [ Time Frame: 32 months ]
    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) [ Time Frame: 32 months ]
    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) [ Time Frame: 32 months ]
    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) [ Time Frame: 32 months ]
    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 [ Time Frame: 32 months ]
    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 [ Time Frame: 32 months ]
    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 [ Time Frame: 32 months ]
    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 [ Time Frame: 32 months ]
    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 [ Time Frame: 32 months ]
    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 [ Time Frame: 32 months ]
    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 [ Time Frame: 32 months ]
    Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL
Official Title  ICMJE 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)
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Hodgkins Lymphoma
  • Chronic Lymphocytic Leukemia
Intervention  ICMJE Drug: JBH492
Anti-CCR7 antibody-drug conjugate (ADC)
Study Arms  ICMJE Experimental: JBH492 single agent
Patients with R/R CLL or NHL
Intervention: Drug: JBH492
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 23, 2020)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 15, 2023
Estimated Primary Completion Date June 15, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Finland,   Germany,   Israel,   Japan,   Korea, Republic of,   Singapore,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04240704
Other Study ID Numbers  ICMJE CJBH492A12101
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP