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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-003893-42 | EudraCT Number |
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Preliminary efficacy seen to date following treatment with AUTO2 has been determined not sufficient to warrant further development
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The purpose of this study is to test the safety and efficacy of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients with Relapsed or Refractory Multiple Myeloma.
The study will consist of 2 phases, a Phase I/dose escalation phase and a Phase II/expansion phase. Patients with relapsed and relapsed or refractory multiple myeloma will be enrolled in both phases of the study. Eligible patients will undergo leukapheresis in order to harvest T cells, which is the starting material for the manufacture of the autologous CAR T product AUTO2. AUTO2 has a dual target BCMA (B cell maturation antigen) and TACI (Transmembrane activator and calcium modulator and cyclophilin ligand interactor). Following pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO2 intravenously as a single or split dose and will then enter a 12-month follow-up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AUTO2 | Experimental | Relapsed or refractory Myeloma patients |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AUTO2 | Biological | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period | Up to 28 days post-infusion | |
| Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT) | 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. | Up to 28 days post-infusion |
| Number of Infused Patients With Best Overall Response | 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 | Up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients for Whom an AUTO2 Product Can be Generated | 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). | Up to 2 years |
| Clinical Benefit Rate |
Not provided
Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Autolus Limited | Sponsor GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VU University Medical Centre Amsterdam | Amsterdam | Netherlands | ||||
| University College London Hospitals NHS Foundation Trust |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37399355 | Derived | Lee L, Lim WC, Galas-Filipowicz D, Fung K, Taylor J, Patel D, Akbar Z, Alvarez Mediavilla E, Wawrzyniecka P, Shome D, Reijmers RM, Gregg T, Wood L, Day W, Cerec V, Ferrari M, Thomas S, Cordoba S, Onuoha S, Khokhar N, Peddareddigari V, Al-Hajj M, Cavet J, Zweegman S, Rodriguez-Justo M, Youg K, Pule M, Popat R. Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy. J Immunother Cancer. 2023 Jun;11(6):e006699. doi: 10.1136/jitc-2023-006699. |
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Screening procedures were performed up to 12 weeks before study treatment administered
Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients were treated with doses from 15 x 10⁶ to 350 x 10⁶ APRIL CAR T Cells.
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| ID | Title | Description |
|---|---|---|
| FG000 | AUTO2 | Relapsed or refractory myeloma patients. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | AUTO2 | Relapsed or refractory myeloma patients |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period | Patients who received at least 1 dose (complete or partial) of AUTO2 therapy (infused set) | Posted | Count of Participants | Participants | Up to 28 days post-infusion |
|
|
From Day 0 until Day 60 post last AUTO2 infusion.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AUTO2 | Relapsed or refractory myeloma patients | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count decreased | Investigations | MedDRA (22.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haematoma | Vascular disorders | MedDRA (22.0) | Non-systematic Assessment |
Early termination leading to small numbers of patients analyzed
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Project Manager | Autolus Ltd | +44 1483 920748 | clinicaltrials@autolus.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 27, 2018 | Sep 4, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 21, 2020 | Sep 4, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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|
Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2 |
| Up to 2 years |
| Duration of Response | 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. | Up to 2 years |
| Time to Disease Progression | 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. | Up to 2 years |
| Progression-free Survival | 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 | Up to 2 years |
| Overall Survival | Descriptive analysis based on number of patients alive at database lock (1-May-2020). | Up to 2 years |
| Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood | Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry. | Up to 2 years |
| London |
| United Kingdom |
| The Christie NHS Foundation Trust | Manchester | M20 4BX | United Kingdom |
| Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust | Newcastle upon Tyne | United Kingdom |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| Primary | Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT) | 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. | Posted | Count of Participants | Participants | Up to 28 days post-infusion |
|
|
|
| Primary | Number of Infused Patients With Best Overall Response | 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 | All patients who received at least 1 dose (complete or partial) of AUTO2 therapy in Phase I of the study were included in this analysis. No patients were enrolled in Phase II as the study was early terminated in Phase I. 2 patients were retreated; their best overall response is presented for this endpoint | Posted | Count of Participants | Participants | Up to 2 years |
|
|
|
| Secondary | Proportion of Patients for Whom an AUTO2 Product Can be Generated | 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). | Posted | Count of Participants | Participants | Up to 2 years |
|
|
|
| Secondary | Clinical Benefit Rate | Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2 | All patients who received at least 1 dose (complete or partial) of AUTO2 therapy in Phase I of the study were included in this analysis. 2 patients were retreated; their best overall response is presented for this endpoint | Posted | Count of Participants | Participants | Up to 2 years |
|
|
|
| Secondary | Duration of Response | 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. | Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the duration of response. The study was terminated early and Phase 2 was not started. | Posted | Up to 2 years |
|
|
| Secondary | Time to Disease Progression | 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. | Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the time to disease progression. The study was terminated early and Phase 2 was not started. | Posted | Up to 2 years |
|
|
| Secondary | Progression-free Survival | 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 | Analysis was not performed due to not enough patients who had a response (VGPR, PR) to justify the progression-free survival. The study was terminated early and Phase 2 was not started. | Posted | Up to 2 years |
|
|
| Secondary | Overall Survival | Descriptive analysis based on number of patients alive at database lock (1-May-2020). | All patients who receive at least 1 dose (complete or partial dose) of AUTO2 therapy | Posted | Count of Participants | Participants | Up to 2 years |
|
|
|
| Secondary | Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood | Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry. | Posted | Count of Participants | Participants | Up to 2 years |
|
|
|
| 11 |
| 6 |
| 11 |
| 11 |
| 11 |
| Metaplastic breast carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Non-systematic Assessment |
|
| Acute myocardial infarction | Cardiac disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Hedache | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Haemophagocytic lymphohistiocytosis | Immune system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Catheter site bruise | General disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| ALT increased | Investigations | MedDRA (22.0) | Non-systematic Assessment |
|
| AST increased | Investigations | MedDRA (22.0) | Non-systematic Assessment |
|
| Blood ALP increased | Investigations | MedDRA (22.0) | Non-systematic Assessment |
|
| Blood creatinine phosphokinase increased | Investigations | MedDRA (22.0) | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (22.0) | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (22.0) | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (22.0) | Non-systematic Assessment |
|
| Respiratory syncytial virus test positive | Investigations | MedDRA (22.0) | Non-systematic Assessment |
|
| Serum ferritin increased | Investigations | MedDRA (22.0) | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Tension headache | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Ear disorder | Ear and labyrinth disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Fluid overload | Metabolism and nutrition disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (22.0) | Non-systematic Assessment |
|
| Enterovirus infection | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment |
|
| External ear cellulitis | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment |
|
| Metapneumovirus infection | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment |
|
| Parvovirus B19 infection | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment |
|
| Pseudomonal bacteraemia | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment |
|
| Rhinovirus infection | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment |
|
| Urinary tract infection enterococcal | Infections and infestations | MedDRA (22.0) | Non-systematic Assessment |
|
Not provided
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |