E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory B cell acute lymphoblastic leukaemia |
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E.1.1.1 | Medical condition in easily understood language |
Acute lymphoblastic leukaemia. A form of cancer of the white blood cells. |
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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 | LLT |
E.1.2 | Classification code | 10000844 |
E.1.2 | Term | Acute lymphoblastic leukaemia |
E.1.2 | System Organ Class | 100000004864 |
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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 |
Phase Ib - To evaluate the safety of AUTO1.
Phase II - To evaluate the clinical efficacy of AUTO1. |
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E.2.2 | Secondary objectives of the trial |
Phase Ib: - To evaluate the feasibility of manufacturing and administering AUTO1. - To evaluate the clinical efficacy of AUTO1 - To evaluate the expansion and persistence of AUTO1
Phase II - To evaluate the clinical efficacy of AUTO1 - To assess the safety and tolerability of AUTO1 - To evaluate the feasibility of manufacturing and administering AUTO1. - To evaluate the expansion and persistence of AUTO1 - To evaluate the duration of B-cell aplasia - To evaluate Patient Reported Outcome and Quality of life assessment - To evaluate health care resource utilisation for the management of AUTO1 related toxicity. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18 or older. 2. Eastern cooperative oncology group (ECOG) performance status of 0 or 1. 3. Relapsed or refractory B-precursor ALL 4. Patients with Philadelphia chromosome positive ALL (Ph+ ALL) are eligible if they are intolerant to or have failed 2 lines of any tyrosine kinase inhibitor (TKI) or 1 line of second-generation TKI, or if TKI therapy is contraindicated. 5. Documentation of CD19 expression on leukaemic blasts 6. Phase Ib: Primary Cohort IA: Presence of ≥5% blasts in BM at screening. Exploratory Cohort IB: MRD-positive defined as ≥10^-4 and <5% blasts in the BM at screening. Phase II: Primary Cohort IIA: Presence of ≥5% blasts in BM at screening. Exploratory Cohort IIB: MRD-positive defined as ≥10^-4 and <5% blasts in the BM at screening or isolated EM disease with the exception of CNS disease at screening. 7. Adequate renal, hepatic, pulmonary, and cardiac function. |
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E.4 | Principal exclusion criteria |
1. Phase Ib (Cohort IA and Cohort IB) and Phase II Cohort IIA only: ALL with isolated EM disease. 2. Diagnosis of Burkitt's leukaemia/lymphoma according to World Health Organization (WHO) classification or chronic myelogenous leukaemia lymphoid blast crisis. 3. History or presence of clinically relevant CNS pathology. 4. Presence of CNS-3 disease or CNS-2 disease with neurological changes. 5. Presence of active or uncontrolled fungal, bacterial, viral, or other infection requiring systemic antimicrobials for management. 6. Active or latent Hepatitis B virus or active Hepatitis C virus 7. Human Immunodeficiency Virus (HIV), HTLV-1, HTLV-2, syphilis positive test 9. Prior CD19 targeted therapy other than blinatumomab. Patients who have experienced Grade 3 or higher neurotoxicity following blinatumomab. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase Ib: Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after AUTO1 infusion.
Phase II: Overall response rate (ORR) defined as proportion of patients achieving complete response [CR] or complete response with incomplete recovery of counts [CRi]. |
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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) |
Phase Ib: - Proportion of enrolled patients for whom an AUTO1 product can be manufactured and administered as per protocol. - Overall response rate (ORR) defined as proportion of patients achieving complete response [CR] or complete response with incomplete recovery of counts [CRi]. - Proportion of patients achieving MRD-negative CR - Detection of CAR T cells measured in the peripheral blood and bone marrow (BM).
Phase II: - Duration of response (DoR). - Relapse Free Survival (RFS). - Event Free Survival (EFS). - Progression free survival (PFS). - Overall Survival (OS). - Proportion of patients achieving MRD-negative CR. - Incidence of CD19 negative relapse - Frequency and severity of adverse events (AEs) and serious adverse events (SAEs). - Incidence and duration of severe hypogammaglobulinaemia. - Proportion of enrolled patients for whom an AUTO1 product can be manufactured and administered. - Detection of CAR T cells measured in the peripheral blood and BM. - Depletion of circulating B cells. - Changes over time in quality of life scores. |
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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 | Yes |
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 |
To evaluate further safety. |
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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
| 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
United States |
Spain |
United Kingdom |
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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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LVLS is expected to be 24 months after the last patient has received AUTO1 infusion. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 21 |