E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients who have been treated for a B cell hematological malignancy in a Novartis sponsored or supported study of CD19 directed CAR T-Cell treatment are enrolled in this study following completion or early discontinuation from a Novartis sponsored or supported study or managed access program of CD19 directed CAR T-Cell treatment. |
|
E.1.1.1 | Medical condition in easily understood language |
Patients who have been treated in a Novartis sponsored or supported study with a CD19 directed chimeric antigen receptor (CAR) T-cell treatment for a B cell malignancy |
|
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 | 20.0 |
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) |
|
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) |
|
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 |
- To monitor all patients exposed to CD19 directed CAR T-cells (CD19 CART) for 15 years following last CD19 CART (e.g. CTL019) infusion to assess the risk of delayed adverse events (AEs). |
|
E.2.2 | Secondary objectives of the trial |
- Monitor the persistence of CD19 CAR transgene
- Monitor for replication competent lentivirus (RCL)
- Assess the long-term efficacy of CD19 CART |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- All patients who have received CD19 CAR T-cell therapy, murine (CTL019) and/or humanized (CTL119) CD19-directed CAR T cell treatment, manufactured by Novartis or Penn and participated in a Novartis or Penn sponsored treatment protocol or a Novartis managed access program. All patients will be included upon completion of the core study or early discontinuation
- Patients who have provided informed consent for the long term follow up study prior to their study participation .
|
|
E.4 | Principal exclusion criteria |
- There are no specific exclusion criteria for this study.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with listed categories:
- New malignancies
- Incidence/exacerbation of pre-existing neurologic disorder
- New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder
- New incidence of a hematologic disorder |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time Frame: 3 monthly until year 1, 6 monthly until year 5, yearly until year 15.
|
|
E.5.2 | Secondary end point(s) |
-Proportion of patients with detectable CD19 CAR transgene levels in peripheral blood by q-PCR at pre- specified post CD19 CART infusion time points
- Proportion of patients with detectable RCL by VSV-G
- Proportion of patients who relapse or progress among patients who had not relapsed or progressed at study entry/re-entry; Incidence of death.
- Absolute B- and T- lymphocyte count
- Height and weight, Tanner staging, menstrual cycle status |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time Frame: 3 monthly until year 1, 6 monthly until year 5, yearly until year 15.
|
|
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Australia |
Austria |
Belgium |
Canada |
France |
Germany |
Italy |
Netherlands |
Norway |
United States |
|
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
|
The end of the LTFU study for each individual patient will be 15 years after the date of patients’ last infusion of CD19 CART. 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. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 20 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |