APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma (APRIL)
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|ClinicalTrials.gov Identifier: NCT03287804|
Recruitment Status : Terminated (Preliminary efficacy seen to date following treatment with AUTO2 has been determined not sufficient to warrant further development)
First Posted : September 19, 2017
Results First Posted : October 23, 2020
Last Update Posted : October 23, 2020
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Biological: AUTO2||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 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 AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients With Relapsed or Refractory Multiple Myeloma|
|Actual Study Start Date :||May 5, 2017|
|Actual Primary Completion Date :||September 5, 2019|
|Actual Study Completion Date :||September 5, 2019|
Relapsed or refractory Myeloma patients
AUTO2 (APRIL CAR T Cells) Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with doses from 15 x 10⁶ to 350 x 10⁶ APRIL CAR T Cells.
Following Phase 2 dose determination patients will be treated with selected dose of APRIL CAR T Cells
- Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period [ Time Frame: Up to 28 days post-infusion ]
- Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT) [ Time Frame: Up to 28 days post-infusion ]
Dose limiting toxicity was defined as:
Any new non-hematological AE of Grade 3 or higher toxicity using the NCI CTCAE (Version 4.03), which is probably or definitely related to AUTO2 therapy, which occurs within the DLT evaluation period, and which fails to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; A Grade 4 CRS; Any other reason for activation of the safety switch after receiving AUTO2; Any other fatal event (Grade 5) or life-threatening event (Grade 4) that cannot be managed with conventional supportive measures or which in the opinion of the SEC necessitates dose reduction or other modification to trial treatment to avoid a similar hazard in future patients. Effort should be made to perform an autopsy in case of fatal event where the aetiology is unclear; Any event that in the opinion of treating investigators and/or Medical Monitor puts the patient at undue risk may also be considered a DLT.
- Number of Infused Patients With Best Overall Response [ Time Frame: Up to 2 years ]Best overall response was defined as stringent complete response + complete response + very good partial response + partial response following treatment with AUTO2. Response Criteria Per IMWG Consensus Recommendations
- Proportion of Patients for Whom an AUTO2 Product Can be Generated [ Time Frame: Up to 2 years ]Feasibility of product generation was examined by assessing the number of AUTO2 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients registered).
- Clinical Benefit Rate [ Time Frame: Up to 2 years ]Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2
- Duration of Response [ Time Frame: Up to 2 years ]Calculated from the date of first observation of sCR, CR, VGPR or PR to the date of disease progression, relapse or death, for patients who were considered responders (achieved at least PR). Patients who had not progressed, relapsed or died will be censored at the last adequate disease assessment.
- Time to Disease Progression [ Time Frame: Up to 2 years ]Calculated from the date of AUTO2 treatment to the date of progression. Patients who had not progressed, relapsed or died without progression/relapse will be censored at the last adequate disease assessment.
- Progression-free Survival [ Time Frame: Up to 2 years ]Calculated from the date of AUTO2 treatment to the date of progression or death. Patients who have not progressed or relapsed was censored at the last adequate disease assessment
- Overall Survival [ Time Frame: Up to 2 years ]Descriptive analysis based on number of patients alive at database lock (1-May-2020).
- Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood [ Time Frame: Up to 2 years ]Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.
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): NCT03287804
|VU University Medical Centre Amsterdam|
|University College London Hospitals NHS Foundation Trust|
|London, United Kingdom|
|The Christie NHS Foundation Trust|
|Manchester, United Kingdom, M20 4BX|
|Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust|
|Newcastle upon Tyne, United Kingdom|
|Study Director:||Autolus Limited||Sponsor GmbH|