CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell Acute Lymphoblastic Leukemia (ALL) (AMELIA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03289455|
Recruitment Status : Completed
First Posted : September 21, 2017
Results First Posted : February 1, 2021
Last Update Posted : February 1, 2021
|Condition or disease||Intervention/treatment||Phase|
|B Acute Lymphoblastic Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Refractory Childhood Acute Lymphoblastic Leukemia B-cell Acute Lymphoblastic Leukemia||Biological: AUTO3 (CD19/22 CAR T cells||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Single-Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity Of AUTO3, a CAR T Cell Treatment Targeting CD19 And CD22 in Paediatric And Young Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia|
|Actual Study Start Date :||June 26, 2017|
|Actual Primary Completion Date :||May 18, 2020|
|Actual Study Completion Date :||May 18, 2020|
Paediatric patients with relapse or refractory B-cell ALL
Biological: AUTO3 (CD19/22 CAR T cells
Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with 1 to 5.0 x 10⁶/kg CD19/CD22 Chimeric Antigen Receptor (CAR) positive T cells as a single or split dose.
- Number of Patients With Grade 3-5 Toxicities Occurring Within the Dose Limiting Toxicity (DLT) Period of AUTO3 Infusion [ Time Frame: Within 30 days (+/- 3 days) after the last dose of AUTO3. ]
- Number of Patients With Dose Limiting Toxicity (DLT) of AUTO3 [ Time Frame: Within 30 days (+/- 3 days) after the last dose of AUTO3. ]DLT was defined as i) any new non-hematological adverse event (AE) of Grade 3 or higher toxicity using the NCI CTCAE (version 5.0), which was probably or definitely related to AUTO3 therapy, which occurred within the DLT evaluation period, and which failed to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; ii) Grade 4 cytokine release syndrome (CRS) or neurotoxicity, cerebral edema, or Grade 3 neurotoxicity (including cerebral edema) that lasted >72 hours; iii) Grade >3 disseminated intravascular coagulation; iv) Grade >2 infusion reaction; v) Any other fatal event (Grade 5) or life-threatening event (Grade 4) that could not be managed with conventional supportive measures or which in the opinion of the Safety Evaluation Committee (SEC) necessitated dose reduction or other modification to trial treatment to avoid a similar hazard in future patients.
- Number of Patients Achieving Morphological Remission (Complete Response(CR) or Complete Response With Incomplete Count Recovery (CRi) and Minimal Residual Disease (MRD)-Negative Response in the Bone Marrow (PCR)). [ Time Frame: Within 30 days (+/- 3 days) post AUTO3 infusion ]Morphological response evaluations were based on the response criteria for ALL according to the NCCN guidelines version 2.2014. Minimal residual disease-negative status was achieved if MRD was <10^-4 (0.01%) by PCR amplification of individual rearrangements of Ig genes and/or flow cytometry MRD testing.
- Feasibility of Generating AUTO3: Number of Patients' Cells Successfully Manufactured as a Proportion of the Number of Patients Undergoing Leukapheresis [ Time Frame: Up to 8 weeks post leukapheresis ]Feasibility of product generation was examined by assessing the number of AUTO3 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients screened).
- Event-Free Survival (EFS) by Morphological Analysis [ Time Frame: Up to 2 years ]Time from date of first AUTO3 infusion until the earliest of treatment failure (defined as not achieving CR/CRi post AUTO3 infusion / no response), morphological relapse, or death due to any cause, whichever occurred first.
- Number of Patients With CD19- and/or CD22-negative Relapse [ Time Frame: Up to 2 years ]
- Relapse-Free Survival (RFS) by Morphological Analysis [ Time Frame: Up to 2 years ]Time from first achievement of morphological CR/CRi post AUTO3 treatment until the earliest of morphological relapse, or death due to any cause, whichever occurred first.
- Overall Survival (OS) [ Time Frame: Up to 2 years after the last patient was infused ]Calculated from the date of AUTO3 treatment to the date of death anytime post AUTO3 infusion. Patients who had not died were censored at the date of last contact.
- Expansion of AUTO3 Following Adoptive Transfer [ Time Frame: Up to 2 years ]Expansion of AUTO3 was measured as the median peak (Cmax) of transgene levels in the peripheral blood after AUTO3 infusion
- Persistence of AUTO3 Following Adoptive Transfer [ Time Frame: Up to 2 years ]
Persistence of AUTO3 was measured by quantitative polymerase chain reaction (qPCR) and/or flow cytometry at a range of time points in the peripheral blood and the bone marrow.
Persistence was defined as the timepoint in days of last detectable CAR T cell by qPCR or last assessment if zero copies per μg DNA (whichever occurred later) before morphological relapse (Tlast).
- Duration of B Cell Aplasia [ Time Frame: Up to 2 years ]Depletion of circulating B cells assessed by flow cytometry at a range of time points in the peripheral blood
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03289455
|Great Ormond Street Hospital for Children NHS Foundation Trust|
|London, United Kingdom|
|University College London Hospitals NHS Foundation Trust|
|London, United Kingdom|
|Royal Manchester Children's Hospital|
|Manchester, United Kingdom|