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Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL)

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ClinicalTrials.gov Identifier: NCT04240704
Recruitment Status : Recruiting
First Posted : January 27, 2020
Last Update Posted : November 3, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Non-Hodgkins Lymphoma Chronic Lymphocytic Leukemia Drug: JBH492 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 7, 2020
Estimated Primary Completion Date : June 14, 2023
Estimated Study Completion Date : June 14, 2023


Arm Intervention/treatment
Experimental: JBH492 single agent Drug: JBH492
Anti-CCR7 antibody-drug conjugate (ADC)




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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 Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. 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

  5. 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)

  6. 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)

  7. 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)

  8. 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)

  9. 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)

  10. 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)

  11. Incidence of anti-JBH492 antibodies [ Time Frame: 32 months ]
    Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies)



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 > 4 weeks before enrollment. 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.
  • Impaired cardiac function or clinically significant cardiac disease
  • Known history of Human Immunodeficiency Virus (HIV) infection
  • Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection

Other inclusion and exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04240704


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Arizona
Mayo Clinic Arizona Recruiting
Phoenix, Arizona, United States, 85054
Contact: Deborah Gallagher    480-342-2545    Gallagher.Deborah@mayo.edu   
Principal Investigator: Allison Rosenthal         
United States, Minnesota
Mayo Clinic Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Jenny Newton    507-538-2155    Newton.Jennifer@mayo.edu   
Principal Investigator: Grzegorz Nowakowski         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Katelyn Gauger    414-805-5249    kgauger@mcw.edu   
Principal Investigator: Timothy Fenske         
Israel
Novartis Investigative Site Recruiting
Tel Aviv, Israel, 6423906
Japan
Novartis Investigative Site Recruiting
Chuo ku, Tokyo, Japan, 104 0045
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169608
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04240704    
Other Study ID Numbers: CJBH492A12101
First Posted: January 27, 2020    Key Record Dates
Last Update Posted: November 3, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
CLL
NHL
CCR7
JBH492
ADC
Chronic Lymphocytic Leukemia
Non-Hodgkins Lymphoma
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell