E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transplant-eligible relapsed or refractory (R/R) aggressive B-cell Non Hodgkin Lymphoma (B-NHL) |
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E.1.1.1 | Medical condition in easily understood language |
A cancer of B-cells, a type of white blood cell responsible for producing Antibodies |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029593 |
E.1.2 | Term | Non-Hodgkin's lymphoma NOS |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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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 primary objective of the study is to compare the efficacy in subjects treated with JCAR017 versus subjects treated according to standard of care (SOC) defined as event-free survival (EFS). |
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E.2.2 | Secondary objectives of the trial |
The key secondary objectives are to compare the efficacy in subjects treated with JCAR017 versus subjects treated according to SOC defined as complete response rate (CRR), progression-free survival (PFS) and overall survival (OS).
- To compare other parameters of efficacy, defined as duration of response (DoR), overall response rate (ORR), PFS on next line of treatment (PFS-2)
- To compare efficacy rates (EFS, PFS, OS) at 6, 12, 24 and 36months after randomization
- To compare the safety defined as type and frequency of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities
- To compare the safety and efficacy in clinical, histological and molecular subgroups
- To compare hospital resource utilization (HRU)
- To describe the rate of completion of high dose chemotherapy (HDCT) and hematopoietic stem cell transplant (HSCT)
- To assess the response 3 months after-HSCT |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF).
2. ECOG performance status ≤ 1.
3. Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or transformed indolent NHL), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma [DHL/THL]) primary mediastinal (thymic) large B-cell lymphoma (PMBCL), T cell/histiocyte-rich large B-cell lymphoma (THRBCL) or follicular lymphoma grade 3B (FL3B). Enough tumor material must be available for confirmation by central pathology.
4. Refractory or relapsed within 12 months from CD20 antibody and anthracycline containing first line therapy.
5. [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion per Lugano criteria at screening (Deauville score 4 or 5).
6. Adequate organ function.
7. Participants must agree to use effective contraception
Please refer to protocol for other inclusion criteria. |
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E.4 | Principal exclusion criteria |
1. Subjects not eligible for hematopoietic stem cell transplantation (HSCT)
2. Subjects planned to undergo allogeneic stem cell transplantation.
3. Subjects with primary cutaneous large B-cell lymphoma, EBV (Epstein-Barr virus) positive DLBCL, Burkitt lymphoma or transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (Richter transformation).
4. Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the subject has been free of the disease for ≥ 2 years with the exception of the following noninvasive malignancies: - Basal cell carcinoma of the skin - Squamous cell carcinoma of the skin - Carcinoma in situ of the cervix - Carcinoma in situ of the breast - Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative. - Other completely resected stage 1 solid tumor with low risk for recurrence
5. Treatment with any prior gene therapy product.
6. Subjects who have received previous CD19-targeted therapy.
7. Subjects with active hepatitis B, or active hepatitis C are excluded. Subjects with negative polymerase chain reaction (PCR) assay for viral load for hepatitis B or C are permitted. Subjects positive for hepatitis B surface antigen and/or anti-hepatitis B core antibody with negative viral load are eligible and should be considered for prophylactic antiviral therapy. Subjects with a history of or active human immunodeficiency virus (HIV) are excluded.
8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
9. Active autoimmune disease requiring immunosuppressive therapy.
10. History of any one of the following cardiovascular conditions within the past 6 months prior to signing the ICF: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
11. History or presence of clinically relevant central nervous system (CNS) pathology.
12. Pregnant or nursing (lactating) women.
Please refer to protocol for full exclusion criteria.
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E.5 End points |
E.5.1 | Primary end point(s) |
Event-free survival (EFS): Time from randomization to death from any cause, progressive disease (PD), failure to achieve complete response (CR) or partial response (PR) or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 3 years post-randomization |
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E.5.2 | Secondary end point(s) |
1. Complete response rate (CRR): Percentage of subjects achieving a complete response (CR).
2. Progression-free survival (PFS): Time from randomization to PD, or death from any cause, whichever occurs first.
3. Overall survival (OS): Time from randomization to time of death due to any cause.
Secondary Efficacy:
1. Overall response rate (ORR): Percentage of subjects achieving an objective response of partial response (PR) or better.
2. Duration of response (DOR): Time from first response to disease progression, start of new antineoplastic therapy due to efficacy concerns or death from any cause.
3. PFS-2: Time from randomization to second objective disease progression or death from any cause, whichever is first.
4. EFS rate Percentage of subjects free of any PFS event at fixed timepoints
5. PFS rate Percentage of subjects free of any PFS event at fixed timepoints
6. OS rate Percentage of subjects alive at fixed timepoints
See protocol for all study endpoints |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key Secondary Efficacy: 1 and 2 - Up to 3 years post-randomization 3 - Up to last subject last visit
Secondary Efficacy: 1, 2, 3 - Up to 3 years post-randomization 4, 5, 6 - At 6, 12, 24 and 36months post-randomization |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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) | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Immunochemotherapy followed by HDCT and HSCT |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 16 |
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 |
Belgium |
Canada |
France |
Germany |
Italy |
Japan |
Netherlands |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 Trial is defined as either the date of the last visit of the last subject to complete the post-treatment follow-up, or the date when the last subject enters the LTFU study, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as pre-specified in the protocol, whichever is the later date. |
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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 | 2 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |