E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
All patients who have been treated with chimeric antigen receptor (CAR) T-cell therapy in the context of a prior Novartis sponsored or supported study for any indication. |
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E.1.1.1 | Medical condition in easily understood language |
Patients who have been treated in a Novartis sponsored or supported study with chimeric antigen receptor (CAR) T-cell treatment. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003917 |
E.1.2 | Term | B-cell type acute leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003899 |
E.1.2 | Term | B-cell lymphoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this study is to monitor all patients exposed to CAR T-cells (CAR-T) for 15 years following last CAR-T (e.g.CTL019) infusion to assess the risk of delayed adverse events (AEs) and assess long term efficacy, including vector persistence. Primary objective is: to describe selected, delayed AEs that are suspected to be related to previous CAR T-cell therapy as outlined in current Health Authority guidelines |
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E.2.2 | Secondary objectives of the trial |
1 • Monitor the persistence of modified T-cells in peripheral blood 2 • Monitor for RCL (Replication Competent Lentivirus) 3 • Assess the long-term efficacy of CAR-T 4 • Monitor lymphocyte levels 5 • Describe the growth, development, and female reproductive status for patients who were aged < 18 years at the time of the initial CAR-T infusion
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patients must have received CAR-T therapy within one of the following: • Novartis or Penn sponsored CAR-T treatment trials where CAR-T was given as monotherapy or as combination therapy. • Novartis managed access programs outside of the commercial setting, i.e. where CAR-T therapy was intended to be given in the setting of a Novartis or Penn sponsored CAR-T treatment trial 2.Patients must provide informed consent prior to their entry into this study.
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E.4 | Principal exclusion criteria |
- There are no specific exclusion criteria for this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with events in each of the following categories: • New secondary malignancies • New serious infections, • New incidence of serious neurologic disorder, • New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder, • New incidence of a hematologic disorder • Other adverse events considered related to CAR T cell therapy
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1- Proportion of patients with detectable CAR transgene levels in peripheral blood by q-PCR at pre-specified time points 2- Proportion of patients with detectable RCL by VSV-G q-PCR in peripheral blood at pre-specified time points 3- Proportion of patients who relapse or progress among patients who had not relapsed or progressed at study entry/re-entry and Incidence of death 4- B and T lymphocyte count 5-Height and weight, Tanner staging, menstruation status |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Long-term follow-up study |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 58 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Singapore |
Switzerland |
Hong Kong |
Taiwan |
Australia |
Austria |
Belgium |
Brazil |
Canada |
China |
Czechia |
Denmark |
Finland |
France |
Germany |
Greece |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Norway |
Saudi Arabia |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the LTFU study for each individual patient will be 15 years after the date of patients’ last infusion of prior Novartis sponsored or supported CAR-T therapy study. The end of study as a whole is defined as the last patient’s last visit (LPLV), which is the last patient’s last evaluation (visit Year 15), or the time of premature withdrawal. All patients who complete the LTFU study will be followed for survival every 6 months until the end of the LTFU study.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 16 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 20 |
E.8.9.2 | In all countries concerned by the trial months | 6 |