Trial Outcomes & Findings for CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell Acute Lymphoblastic Leukemia (ALL) (NCT NCT03289455)

NCT ID: NCT03289455

Last Updated: 2021-02-01

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Within 30 days (+/- 3 days) after the last dose of AUTO3.

Results posted on

2021-02-01

Participant Flow

23 patients were screened, 20 patients leukapheresed and 15 patients were pre-conditioned with cyclophosphamide and fludarabine and infused with AUTO3 at 3 different dose levels.

Participant milestones

Participant milestones
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Overall Study STARTED	4	5	6
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	4	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Overall Study Death	1	0	0
Overall Study Sponsor decision due to covid19 restrictions	0	1	0
Overall Study No CART persistence in MRD negativity. Patient proceeded with HSCT	0	0	1
Overall Study Progressive disease	3	4	5

Baseline Characteristics

CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell Acute Lymphoblastic Leukemia (ALL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=6 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells	Total n=15 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United Kingdom	4 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	15 participants n=4 Participants
Karnofsky/Lansky score	95 percentage n=5 Participants	90 percentage n=7 Participants	100 percentage n=5 Participants	90 percentage n=4 Participants

PRIMARY outcome

Timeframe: Within 30 days (+/- 3 days) after the last dose of AUTO3.

Population: Patients who received at least 1 (complete or partial) dose of AUTO3 (infused set)

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=6 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Number of Patients With Grade 3-5 Toxicities Occurring Within the Dose Limiting Toxicity (DLT) Period of AUTO3 Infusion	4 Participants	4 Participants	6 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=6 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Number of Patients With Dose Limiting Toxicity (DLT) of AUTO3	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Within 30 days (+/- 3 days) post AUTO3 infusion

Population: Patients who received at least 1 (complete or partial) dose of AUTO3 (infused set).

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.

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=6 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
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)).	3 Participants	5 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 8 weeks post leukapheresis

Population: Patients who underwent leukapheresis. This outcome is measured before patients received infusion with AUTO3. Therefore, no split by dose cohort can be provided.

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).

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=20 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Feasibility of Generating AUTO3: Number of Patients' Cells Successfully Manufactured as a Proportion of the Number of Patients Undergoing Leukapheresis	19 Participants	—	—

SECONDARY outcome

Timeframe: Up to 2 years

Population: Patients who received at least 1 (complete or partial) dose of AUTO3 (infused set)

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.

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=6 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Event-Free Survival (EFS) by Morphological Analysis	3.48 months Interval 0.03 to Upper limit of the confidence interval was not reached	12.42 months Interval 3.94 to Upper limit of the confidence interval was not reached	2.79 months Interval 0.03 to Upper limit of the confidence interval was not reached

SECONDARY outcome

Timeframe: Up to 2 years

Population: Patients who received at least 1 (complete or partial dose) of AUTO3 and had morphological relapses

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=2 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=3 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Number of Patients With CD19- and/or CD22-negative Relapse	0 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: Patients who received at least 1 (complete or partial) dose of AUTO3 (infused set)

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.

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=6 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Relapse-Free Survival (RFS) by Morphological Analysis	6.09 months Interval 2.56 to Upper limit of the confidence interval was not reached	11.50 months Interval 3.02 to Upper limit of the confidence interval was not reached	3.98 months Interval 1.87 to Upper limit of the confidence interval was not reached

SECONDARY outcome

Timeframe: Up to 2 years after the last patient was infused

Population: Patients who received at least 1 (complete or partial) dose of AUTO3

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.

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=6 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Overall Survival (OS)	10.17 months Interval 2.3 to The upper limit of the confidence interval was not reached	25.20 months Interval 4.34 to The upper limit of the confidence interval was not reached	NA months Interval 4.07 to The median was not estimable. The upper limit of the confidence interval was not reached

SECONDARY outcome

Timeframe: Up to 2 years

Population: Patients who received at least 1 (complete or partial) dose of AUTO3 and had evaluable cellular kinetics data (who had at least 1 cellular kinetics concentration post AUTO3 infusion above the lower limit of quantitation) (cellular kinetics analysis set)

Expansion of AUTO3 was measured as the median peak (Cmax) of transgene levels in the peripheral blood after AUTO3 infusion

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Expansion of AUTO3 Following Adoptive Transfer	10240 vector copies/ug DNA Interval 5690.0 to 37000.0	102000 vector copies/ug DNA Interval 34800.0 to 127000.0	79800 vector copies/ug DNA Interval 13200.0 to 104000.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Persistence of AUTO3 Following Adoptive Transfer	41.7 days Interval 19.8 to 256.8	343.7 days Interval 62.7 to 538.9	24.3 days Interval 18.8 to 570.8

SECONDARY outcome

Timeframe: Up to 2 years

Population: Patients who received at least 1 (complete or partial) dose of the pre-conditioning regimen (safety set)

Depletion of circulating B cells assessed by flow cytometry at a range of time points in the peripheral blood

Outcome measures

Outcome measures
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 Participants Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 Participants All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=6 Participants Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Duration of B Cell Aplasia	NA months B cell aplasia from the database was inconclusive because the total lymphocytes from the peripheral blood analyzed by flow cytometry were not collected systematically	NA months B cell aplasia from the database was inconclusive because the total lymphocytes from the peripheral blood analyzed by flow cytometry were not collected systematically	NA months B cell aplasia from the database was inconclusive because the total lymphocytes from the peripheral blood analyzed by flow cytometry were not collected systematically

Adverse Events

1x10^6 CD19/CD22 CAR-positive T Cells/kg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 3 deaths

3x10^6 CD19/CD22 CAR-positive T Cells/kg

Serious events: 2 serious events

Other events: 5 other events

Deaths: 3 deaths

5x10^6 CD19/CD22 CAR-positive T Cells/kg

Serious events: 3 serious events

Other events: 6 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	1x10^6 CD19/CD22 CAR-positive T Cells/kg n=4 participants at risk Patients assigned in this Cohort received actual doses of 0.3 to 2x10\^6 CD19/CD22 CAR-positive T cells	3x10^6 CD19/CD22 CAR-positive T Cells/kg n=5 participants at risk All patients assigned in this Cohort received actual doses of 3x10\^6 CD19/CD22 CAR-positive T cells	5x10^6 CD19/CD22 CAR-positive T Cells/kg n=6 participants at risk Patients assigned in this Cohort received actual doses of 4.3 to 5x10\^6 CD19/CD22 CAR-positive T cells
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	20.0% 1/5 • Number of events 1 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	33.3% 2/6 • Number of events 2 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/4 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	20.0% 1/5 • Number of events 1 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	16.7% 1/6 • Number of events 1 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first
Blood and lymphatic system disorders Neutropenia	0.00% 0/4 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	20.0% 1/5 • Number of events 1 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	33.3% 2/6 • Number of events 2 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/4 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	20.0% 1/5 • Number of events 1 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	33.3% 2/6 • Number of events 2 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first
General disorders Pyrexia	0.00% 0/4 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	0.00% 0/5 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	16.7% 1/6 • Number of events 1 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first
Infections and infestations Cellulitis	0.00% 0/4 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	0.00% 0/5 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	16.7% 1/6 • Number of events 1 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first
Nervous system disorders Encephalopathy	25.0% 1/4 • Number of events 1 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	0.00% 0/5 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	0.00% 0/6 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first
Nervous system disorders Seizure	0.00% 0/4 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	0.00% 0/5 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first	16.7% 1/6 • Number of events 1 • From AUTO3 infusion (Day 0) until the end of study (2 years after last patient dosed) or withdrawal, whichever occurred first

Other adverse events

Additional Information

Clinical Project Manager

Autolus Ltd

Phone: +44 1483 920748

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60