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History of Changes for Study: NCT04240704
Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL)
Latest version (submitted June 1, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 23, 2020 None (earliest Version on record)
2 May 12, 2020 Study Status and Eligibility
3 May 26, 2020 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 June 17, 2020 Study Status
5 June 19, 2020 Contacts/Locations and Study Status
6 July 22, 2020 Study Status and Contacts/Locations
7 August 4, 2020 Study Status
8 September 8, 2020 Study Status
9 November 2, 2020 Study Status
10 February 23, 2021 Study Status and Contacts/Locations
11 April 14, 2021 Study Status and Contacts/Locations
12 June 1, 2021 Study Status and Contacts/Locations
13 July 26, 2021 Study Status
14 December 3, 2021 Study Status
15 June 1, 2022 Contacts/Locations, Study Status, Eligibility, Arms and Interventions, Study Design, Study Description and Study Identification
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Study NCT04240704
Submitted Date:  January 23, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: CJBH492A12101
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)
Secondary IDs:
Open or close this module Study Status
Record Verification: January 2020
Overall Status: Not yet recruiting
Study Start: March 25, 2020
Primary Completion: December 30, 2022 [Anticipated]
Study Completion: December 30, 2022 [Anticipated]
First Submitted: January 23, 2020
First Submitted that
Met QC Criteria:
January 23, 2020
First Posted: January 27, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
January 23, 2020
Last Update Posted: January 27, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Novartis Pharmaceuticals
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module 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:
Open or close this module Conditions
Conditions: Non-Hodgkins Lymphoma
Chronic Lymphocytic Leukemia
Keywords: CLL
NHL
CCR7
JBH492
ADC
Chronic Lymphocytic Leukemia
Non-Hodgkins Lymphoma
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 120 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: JBH492 single agent Drug: JBH492
Anti-CCR7 antibody-drug conjugate (ADC)
Open or close this module Outcome Measures
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)
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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.

Open or close this module Contacts/Locations
Central Contact Person: Novartis Pharmaceuticals
Telephone: 1-888-669-6682
Email: novartis.email@novartis.com
Central Contact Backup: Novartis Pharmaceuticals
Telephone: +41613241111
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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