Trial Outcomes & Findings for APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma (NCT NCT03287804)
NCT ID: NCT03287804
Last Updated: 2020-10-23
Results Overview
TERMINATED
PHASE1/PHASE2
12 participants
Up to 28 days post-infusion
2020-10-23
Participant Flow
Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients were treated with doses from 15 x 10⁶ to 350 x 10⁶ APRIL CAR T Cells.
Screening procedures were performed up to 12 weeks before study treatment administered
Participant milestones
| Measure |
AUTO2
Relapsed or refractory myeloma patients.
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
Leukaperesed
|
12
|
|
Overall Study
Started Pre-conditioning Therapy
|
11
|
|
Overall Study
Received Study Treatment
|
11
|
|
Overall Study
COMPLETED
|
1
|
|
Overall Study
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
AUTO2
Relapsed or refractory myeloma patients.
|
|---|---|
|
Overall Study
Death
|
1
|
|
Overall Study
Physician Decision
|
2
|
|
Overall Study
Progressive disease
|
8
|
Baseline Characteristics
APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma
Baseline characteristics by cohort
| Measure |
AUTO2
n=12 Participants
Relapsed or refractory myeloma patients
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
11 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 28 days post-infusionPopulation: Patients who received at least 1 dose (complete or partial) of AUTO2 therapy (infused set)
Outcome measures
| Measure |
AUTO2
n=11 Participants
Relapsed or refractory myeloma patients
|
|---|---|
|
Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 28 days post-infusionDose 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.
Outcome measures
| Measure |
AUTO2
n=11 Participants
Relapsed or refractory myeloma patients
|
|---|---|
|
Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT)
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 2 yearsPopulation: 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
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
Outcome measures
| Measure |
AUTO2
n=11 Participants
Relapsed or refractory myeloma patients
|
|---|---|
|
Number of Infused Patients With Best Overall Response
|
4 Participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsFeasibility 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).
Outcome measures
| Measure |
AUTO2
n=12 Participants
Relapsed or refractory myeloma patients
|
|---|---|
|
Proportion of Patients for Whom an AUTO2 Product Can be Generated
|
12 Participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: 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
Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2
Outcome measures
| Measure |
AUTO2
n=11 Participants
Relapsed or refractory myeloma patients
|
|---|---|
|
Clinical Benefit Rate
|
4 Participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: 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.
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
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: All patients who receive at least 1 dose (complete or partial dose) of AUTO2 therapy
Descriptive analysis based on number of patients alive at database lock (1-May-2020).
Outcome measures
| Measure |
AUTO2
n=11 Participants
Relapsed or refractory myeloma patients
|
|---|---|
|
Overall Survival
|
3 Participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsExpansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.
Outcome measures
| Measure |
AUTO2
n=11 Participants
Relapsed or refractory myeloma patients
|
|---|---|
|
Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood
|
9 Participants
|
Adverse Events
AUTO2
Serious adverse events
| Measure |
AUTO2
n=11 participants at risk
Relapsed or refractory myeloma patients
|
|---|---|
|
Investigations
Neutrophil count decreased
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metaplastic breast carcinoma
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Cardiac disorders
Acute myocardial infarction
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Nervous system disorders
Hedache
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
General disorders
Pyrexia
|
18.2%
2/11 • Number of events 5 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Infections and infestations
Lung infection
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
Other adverse events
| Measure |
AUTO2
n=11 participants at risk
Relapsed or refractory myeloma patients
|
|---|---|
|
Vascular disorders
Haematoma
|
18.2%
2/11 • Number of events 2 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Vascular disorders
Hypotension
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Immune system disorders
Haemophagocytic lymphohistiocytosis
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
General disorders
Catheter site bruise
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
General disorders
Chills
|
36.4%
4/11 • Number of events 4 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
General disorders
Fatigue
|
54.5%
6/11 • Number of events 10 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
General disorders
Oedema peripheral
|
27.3%
3/11 • Number of events 4 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
General disorders
Pyrexia
|
54.5%
6/11 • Number of events 8 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Psychiatric disorders
Hallucination
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Investigations
ALT increased
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Investigations
AST increased
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Investigations
Blood ALP increased
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Investigations
Blood creatinine phosphokinase increased
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Investigations
Gamma-glutamyltransferase increased
|
9.1%
1/11 • Number of events 2 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Investigations
Neutrophil count decreased
|
63.6%
7/11 • Number of events 71 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Investigations
Platelet count decreased
|
18.2%
2/11 • Number of events 12 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Investigations
Respiratory syncytial virus test positive
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Investigations
Serum ferritin increased
|
9.1%
1/11 • Number of events 3 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Blood and lymphatic system disorders
Anaemia
|
81.8%
9/11 • Number of events 31 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Blood and lymphatic system disorders
Neutropenia
|
27.3%
3/11 • Number of events 29 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
18.2%
2/11 • Number of events 7 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.2%
2/11 • Number of events 2 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
36.4%
4/11 • Number of events 5 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.1%
1/11 • Number of events 2 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
27.3%
3/11 • Number of events 3 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Nervous system disorders
Dizziness
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Nervous system disorders
Dysgeusia
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Nervous system disorders
Headache
|
27.3%
3/11 • Number of events 6 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Nervous system disorders
Paraesthesia
|
18.2%
2/11 • Number of events 2 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Nervous system disorders
Tension headache
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Ear and labyrinth disorders
Ear disorder
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Gastrointestinal disorders
Constipation
|
18.2%
2/11 • Number of events 3 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Gastrointestinal disorders
Diarrhoea
|
45.5%
5/11 • Number of events 6 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Gastrointestinal disorders
Dry mouth
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Gastrointestinal disorders
Haematochezia
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Gastrointestinal disorders
Nausea
|
18.2%
2/11 • Number of events 3 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Gastrointestinal disorders
Stomatitis
|
27.3%
3/11 • Number of events 3 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Renal and urinary disorders
Micturition urgency
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Skin and subcutaneous tissue disorders
Rash
|
18.2%
2/11 • Number of events 2 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
27.3%
3/11 • Number of events 6 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
36.4%
4/11 • Number of events 6 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
18.2%
2/11 • Number of events 2 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
27.3%
3/11 • Number of events 3 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Metabolism and nutrition disorders
Dehydration
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Metabolism and nutrition disorders
Fluid overload
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
9.1%
1/11 • Number of events 2 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Infections and infestations
Enterovirus infection
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Infections and infestations
External ear cellulitis
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Infections and infestations
Metapneumovirus infection
|
9.1%
1/11 • Number of events 2 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Infections and infestations
Parvovirus B19 infection
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Infections and infestations
Pseudomonal bacteraemia
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Infections and infestations
Rhinovirus infection
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Infections and infestations
Upper respiratory tract infection
|
18.2%
2/11 • Number of events 2 • From Day 0 until Day 60 post last AUTO2 infusion.
|
|
Infections and infestations
Urinary tract infection enterococcal
|
9.1%
1/11 • Number of events 1 • From Day 0 until Day 60 post last AUTO2 infusion.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60