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Non Hodgkin LymphomaPhase 2TIGER-CTL019NCT04161118

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

A Phase 2 study testing CTL019 in people with Non Hodgkin Lymphoma, run by University of Cologne at 2 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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

Who is it for?
Ages 60 to 80 years
Conditions the study is for
Non Hodgkin Lymphoma
What is being tested?
CTL019
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
2 sitesGermany
Study dates
12 May 2021to 24 Feb 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • DLBCL, leg type
  • Measurable disease:
  • Nodal lesions >15 mm in the long axis, regardless of the length of the short axis, and/or
  • Extranodal lesions (outside lymph node or nodal mass, but including liver and spleen) >10 mm in long AND short axis
  • ECOG performance status 0-2
  • Adequate organ function:
  • Kidney function defined as: i. Serum creatinine estimated glomerular filtration rate GFR ≥ 30mL/min b. Hepatic function defined as: i. ALT and AST ≤ 5 × ULN, except for aNHL-related functional impairment. ii. Bilirubin ≤2.0 mg/dl except for patients with Gilbert syndrome, who may be included if their total bilirubin is ≤3.0 × ULN and direct bilirubin ≤1.5 × ULN OR for aNHL-related functional impairment c. Adequate bone marrow function (regardless of transfusion) defined as: i. WBC ≥2500/µL ii. Absolute neutrophil count (ANC) >1000/µL iii. Platelets ≥50,000/µL iv. Hemoglobin >8.0 g/dl d. Minimum level of pulmonary function defined as: i. No or mild dyspnea (≤ Grade 1) ii. pulse oxygenation ≥ 91% on room air
  • Life expectancy of more than six months
  • Women have to be in menopausal or post-menopausal status or confirmed as not having potential on childbearing
  • Male participants with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods as described in the study protocol

Who cannot join

  • 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
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  • 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:
  • Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or
  • Concomitant medication(s) with a "Known Risk of Torsades de Point" per www.qtdrugs.org that cannot be discontinued or replaced by safe alternative medication.
  • Previous or concurrent malignancy with the following exceptions:
  • Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
  • In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of of recurrence for at least 3 years prior to the study
  • A primary malignancy which has been completely resected and in complete remission for ≥ 3 years
  • Pregnant or nursing (lactating) women and women who are not confirmed to be menopausal/post-menopausal. Or women who are capable of giving birth.
  • Intolerance to the excipients of the tisagenlecleucel cell product
  • Active or history of inflammatory disorders or autoimmune disease that required systemic steroids or immunosuppressive medications, with exception of vitiligo or resolved childhood asthma
  • Active tuberculosis
  • Exposure to any investigational agent(s) within 4 weeks prior to study entry
  • Chemotherapy less than 2 weeks before leukapheresis
  • Simultaneous radiotherapy to tisagenlecleucel infusion (radiotherapy between leukapheresis and day -6 before tisagenlecleucel infusion is permitted)
  • Ongoing necessity for systemic corticosteroids >10mg daily prednisone equivalent. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
  • History of active primary immunodeficiency
  • Major surgery (defined as opening at least one body cavity) within 4 weeks prior to study entry
  • History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening CT scan
  • Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PDL2, anti-CTLA-4 antibodies, other immune checkpoint inhibitors
  • Prior treatment with any anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy.
  • Current treatment within another therapeutic clinical trial with experimental and not approved drugs and treatment combinations
  • Patient's lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate his/her own wishes correspondingly
  • Non-compliance, e.g. due to
  • Drug dependency or substance abuse that would interfere with cooperation with requirements of the trial
  • Refusal of blood products during treatment
  • Change of residence to abroad
  • any similar circumstances that appear to make protocol treatment or long-term follow-up impossible
  • Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator
  • Committal to an institution on judicial or official order

Trial locations and contacts

2 sites in 1 country.

Germany2 sites

  • University of Cologne

    Cologne, 50937

  • Universitätsklinik Essen, Klinik für Hämatologie

    Essen, 45147

Other trials in Germany

About this study

Official title: Phase II Trial of TisaGenlecleucel in Elderly Patients With First-Relapsed or Primary Refractory Aggressive B-cell Non-Hodgkin Lymphoma

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

Read the detailed description

This is a single-arm, prospective, multicenter phase-II trial for elderly patients with aNHL failing 1st-line treatment with immunochemotherapy containing rituximab and anthracycline, who are not eligible for either autologous or allogeneic stem cell transplantation, defined as age > 65 years, or > 60 years old with HCT-CI score >2. This trial evaluates the CMR rate 12 weeks after tisagenlecleucel (CTL019) infusion, the incidence and severity of adverse events, progression-free survival, and overall survival after one and two years after tisagenlecleucel (CTL019).

Being tested
CTL019
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CTL019Drug

    IV Infusion

Study groups in NCT04161118
Study groupRoleWhat they receive
Tisagenlecleucel (CTL019)ExperimentalAll 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.
Receives: Drug: CTL019

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 12 weeks after tisagenlecleucel (CTL019) infusion

Secondary outcomes (3)

  1. Incidence and severity of adverse events (AEs)

    Incidence and severity of adverse events (AEs)

    Measured: From study start to study end (44 months)

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

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

    Measured: Up to two years from study start

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

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

    Measured: Up to two years from study start

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2019
  2. Study start12 May 2021
  3. Primary completion24 Feb 2023
  4. Study completion24 Feb 2023

Why it stopped: Termination of the funding agreement by the financial sponsor of the study. Small number of patients enrolled, none of the planned analyses will be feasible to draw conclusions on the safety or efficacy of the therapy.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04161118
Sponsor's protocol ID
Uni-Koeln-3903
Acronym
TIGER-CTL019
Status last verified
May 2023
First submitted
8 Nov 2019
Last updated
6 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CTL019 in people with Non Hodgkin Lymphoma, run by University of Cologne at 2 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Termination of the funding agreement by the financial sponsor of the study. Small number of patients enrolled, none of the planned analyses will be feasible to draw conclusions on the safety or efficacy of the therapy.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 12 weeks after tisagenlecleucel (CTL019) infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04161118.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.

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