Clinical Trials /

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

NCT04240704

Description:

The purpose of the First-In-Human study is to assess safety, tolerability, pharmacokinetics (PK), immunogenicity and preliminary efficacy of JBH492 as single agent.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CJBH492A12101
  • NCT ID: NCT04240704

Conditions

  • Non-Hodgkins Lymphoma
  • Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
JBH492JBH492 single agent

Purpose

The purpose of the First-In-Human study is to assess safety, tolerability, pharmacokinetics (PK), immunogenicity and preliminary efficacy of JBH492 as single agent.

Trial Arms

NameTypeDescriptionInterventions
JBH492 single agentExperimental
  • JBH492

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 > 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and severity of dose limiting toxicities (DLTs)
Time Frame:32 months
Safety Issue:
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.

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:32 months
Safety Issue:
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).
Measure:Best overall response (BOR)
Time Frame:32 months
Safety Issue:
Description:The best overall response (BOR) is the best reponse recorded in a patient from the start of treatment until disease progression.
Measure:Duration of Response (DOR)
Time Frame:32 months
Safety Issue:
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.
Measure:Progression Free Survival (PFS)
Time Frame:32 months
Safety Issue:
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
Measure:Pharmacokinetics (PK) parameter AUClast
Time Frame:32 months
Safety Issue:
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)
Measure:PK parameter AUCinf
Time Frame:32 months
Safety Issue:
Description:The AUC from time zero to infinity (mass × time × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Measure:PK parameter AUCtau
Time Frame:32 months
Safety Issue:
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)
Measure:PK parameter Cmax and Cmin
Time Frame:32 months
Safety Issue:
Description:The maximum (peak) and minimum observed serum drug concentration (mass × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Measure:PK parameter Tmax
Time Frame:32 months
Safety Issue:
Description:The time to reach maximum (peak) serum drug concentration (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Measure:PK parameter T1/2
Time Frame:32 months
Safety Issue:
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)
Measure:Incidence of anti-JBH492 antibodies
Time Frame:32 months
Safety Issue:
Description:Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • CLL
  • NHL
  • CCR7
  • JBH492
  • ADC
  • Chronic Lymphocytic Leukemia
  • Non-Hodgkins Lymphoma

Last Updated

June 19, 2020