E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CD19+ B cell lymphoma or leukemia |
CD19+ B cells-malignitet |
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E.1.1.1 | Medical condition in easily understood language |
Leukemia and lymphoma, blood cell cancer |
Leukemi och lymfom, blodcancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To evaluate the feasibility and safety of two administrations of CAR T cells to patients with disseminated B cell lymphoma or leukemia. - To evaluate long-term toxicity of CAR T cells by an extended follow-up period (12-24 months) when patients are analyzed even if they have progressed in their disease and/or received another therapy. - To evaluate whether two courses of gemcitabine given in association with CAR T cells can increase the effect of CAR T cell therapy.
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E.2.2 | Secondary objectives of the trial |
- Establish persistence and function of CAR T cells. - To evaluate if FDG-PET MRI is a suitable technique to determine therapy response - Evaluate the level of B cells as a measurement of CAR T cell efficacy. - Evaluate immune profile shifts post treatment as a measurement of CAR T cell function.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Relapsed or refractory CD19+ B-cell lymphoma, leukemia or Hodgkin lymphoma with no other curative treatment option available. 2. Measurable disease 3. All ages 4. Performance status ECOG 0-2 (Appendix IV) 5. Fertile females/male must consent to use highly effective* contraceptives during the participation of the trial 6. Signed informed consent * This study follows the 2014 CTFG guidance document “Recommendations related to contraception and pregnancy testing in clinical trials” (Appendix XII). The patients must consent to use highly effective contraceptives during the participation of the trial. Contraceptive methods considered highly effective by the guidance document are those with a Pearl index <1% when used consistently and correctly. Highly effective contraceptives include combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation via e.g. oral, transdermal or intravaginal administration. Also included are progesterone-only hormonal contraception associated with inhibition of ovulation via e.g. oral, injectable or implantable administration. Other acceptable methods include intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, a vasectomized partner and sexual abstinence. Methods not included are e.g. condoms, diaphragm with spermicide and low-dose progesterone.
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E.4 | Principal exclusion criteria |
1. Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures 2. Patients with primary CNS lymphoma 3. Known human immunodeficiency virus (HIV) infection 4. Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection) 5. Other serious underlying medical conditions, which, in the Investigator’s judgment, could impair the ability of the patient to perform the treatment 6. Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half-lives of that drug, which is longest 7. Pregnancy 8. Patients that do not consent to that tissue and blood samples are stored in a biobank 9. Patients whose cells cannot be manufactured
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E.5 End points |
E.5.1 | Primary end point(s) |
- Registration of the safety profile such as inflammation, fever, pain, changes in blood pressure, pulse and other adverse events. - Tumor response measured as best response and over all response.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Weekly the first 6 weeks, then at 3, 6, 9, 12, 15, 18, 21 and 24 months. |
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E.5.2 | Secondary end point(s) |
- Determination of the level of CAR T cells (mRNA and cells) in blood and biopsies. - Determination of activation markers on CAR T cells such as CD107a. - Determination of tumor size and the tumor marker CD19. - Determination of the levels of circulating B cells. - Determination of the presence of immunological markers in blood and biopsies.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 1 and 3 weeks then at 3, 6, 9, 12, 15, 18, 21 and 24 months. |
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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 | No |
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) | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |