TisaGenlecleucel in Elderly Patients With First-Relapsed or Primary Refractory Aggressive B-cell Non-Hodgkin Lymphoma

NCT04161118 | Terminated Phase 2

• 1 other identifier: Uni-Koeln-3903
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

A phase II trial of TisaGenlecleucel (CTL019) in Elderly Patients with First-Relapsed or Primary Refractory Aggressive B-cell Non-Hodgkin Lymphoma

Conditions

Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Estimation of the efficacy of treatment with tisagenlecleucel (CTL019) in elderly patients with r/r aNHL by measuring the complete metabolic response (CMR) rate 12 weeks after tisagenlecleucel (CTL019) infusion

  Estimation of the efficacy of treatment with tisagenlecleucel (CTL019) in elderly patients with r/r aNHL by measuring the complete metabolic response (CMR) rate 12 weeks after tisagenlecleucel (CTL019) infusion

  12 weeks after tisagenlecleucel (CTL019) infusion

Secondary Outcomes (3)

• Incidence and severity of adverse events (AEs)

  From study start to study end (44 months)

• Progression-free survival (PFS) rates at 1 and 2 year(s)

  Up to two years from study start

• Overall survival (OS) rates at 1 and 2 year(s)

  Up to two years from study start

Study Arms (1)

Tisagenlecleucel (CTL019)

EXPERIMENTAL

All patients will receive a single target dose of 0.6 to 6.0 × 108 of autologous tisagenlecleucel (CTL019) transduced T-cells with a viability of at least 70% administered via IV infusion after optional bridging with chemo- or immunotherapy and lymphodepleting (LD) chemotherapy with cyclophosphamide and fludarabine.

Drug: CTL019

Interventions

CTL019 DRUG

IV Infusion

Tisagenlecleucel (CTL019)

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written, signed and dated informed consent must be obtained prior to participation in the study
• Patients with first relapse of aggressive B-cell Non-Hodgkin Lymphoma (aNHL) within 365 days after rituximab- and anthracycline-containing first-line immunochemotherapy or aNHL refractory to first-line therapy (not achieving a CR or PR), who are ineligible for either autologous or allogeneic stem cell transplantation, defined by age \> 65 years, or \> 60 years with a HCT-CI score \> 2 (https://qxmd.com/calculate/calculator\_108/hematopoietic-cell-transplantation-specific-comorbidity-index-hct-ci) and not older than 80 years.
• Histologically confirmed (by local histopathological assessment) aNHL at relapse or progression due to refractory disease after front line therapy. aNHL is defined by the following list of subtypes:
• DLBCL, NOS (GCB, ABC, centroblastic, immunoblastic, anaplastic)
• FL grade 3B
• T-cell-rich/histiocyte-rich large B-cell lymphoma (T/HRBCL)
• DLBCL associated with chronic inflammation
• Intravascular large B-cell lymphoma
• ALK+ large B-cell lymphoma
• B-cell lymphoma, unclassifiable, (with features intermediate between DLBCL and classical HL)
• High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
• High-grade B-cell lymphoma, NOS
• HHV8+ DLBCL, NOS
• DLBCL transformed from follicular lymphoma
• DLBCL transformed from marginal zone lymphoma

You may not qualify if:

• Patients with Richter's transformation, Burkitt lymphoma, or primary CNS lymphoma (PCNSL)
• Prior treatment with anti-CD19 therapy, adoptive T-cell therapy, or any prior gene therapy product
• Treatment with any lymphoma-directed second-line anticancer therapy prior to enrollment with the exception of intermittent steroid therapy. After enrollment, bridging therapy is permitted for disease control.
• Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated (i.e. patient is asymptomatic) and local treatment was \>4 weeks before enrollment
• Prior allogeneic bone marrow transplantation (HSCT)
• Active hepatitis B, hepatitis C, or hepatitis E infection
• HIV-positive patients
• Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• Any of the following cardiovascular conditions:
• Unstable angina, myocardial infarction, coronary artery bypass graft (CABG), or stroke within 6 months prior to screening,
• LVEF \<45% as determined by ECHO at screening except for aNHL-related functional impairment,
• NYHA functional class III or IV (Chavey et al. 2001) at screening,
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II) and third degree AV block, unless adequately controlled by pacemaker implantation,
• Resting QTcF ≥450 msec (male) or ≥460 msec (female) at screening or inability to determine the QTcF interval,
• Risk factors for Torsades de Point (TdP), including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia, or any of the following:

Sponsors & Collaborators

• University of Cologne: lead
• Novartis: collaborator

Study Sites (2)

University of Cologne

Cologne, 50937, Germany

Location

Universitätsklinik Essen, Klinik für Hämatologie

Essen, 45147, Germany

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

tisagenlecleucel

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Trial Chairman

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: November 13, 2019
• Study Start: May 12, 2021
• Primary Completion: February 24, 2023
• Study Completion: February 24, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)