Trial Outcomes & Findings for Anti-CD19 White Blood Cells for Children and Young Adults With B Cell Leukemia or Lymphoma (NCT NCT01593696)

Last Updated: 2020-08-31

Results Overview

Participants with B cell malignancies who received preparative chemotherapy followed by CD19 CAR T-cells with \< Grade 4 cytokine release syndrome.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

53 participants

Primary outcome timeframe

Beginning of preparative regimen through Day 28 after CD19 CAR infusion

Results posted on

2020-08-31

Participant Flow

Participant milestones

Participant milestones
Measure	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion. Follow-up through at least 28 days after CD19 CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion. Follow-up through at least 28 days after CD19 CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion. Follow-up through at least 28 days after CD19 CAR infusion.	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion. Follow-up through at least 28 days after CD19 CAR infusion.
Dose Escalation STARTED	16	5	0	0
Dose Escalation Prior Transplant	7	1	0	0
Dose Escalation No Prior Transplant	9	4	0	0
Dose Escalation COMPLETED	14	5	0	0
Dose Escalation NOT COMPLETED	2	0	0	0
Dose Expansion STARTED	0	0	16	16
Dose Expansion COMPLETED	0	0	15	16
Dose Expansion NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion. Follow-up through at least 28 days after CD19 CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion. Follow-up through at least 28 days after CD19 CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion. Follow-up through at least 28 days after CD19 CAR infusion.	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion. Follow-up through at least 28 days after CD19 CAR infusion.
Dose Escalation Progressive Disease	2	0	0	0
Dose Expansion Fungal infection	0	0	1	0

Baseline Characteristics

Anti-CD19 White Blood Cells for Children and Young Adults With B Cell Leukemia or Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) n=5 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Total n=53 Participants Total of all reporting groups
Age, Categorical <=18 years	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants	10 Participants n=4 Participants	38 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	15 Participants n=21 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	0 Participants n=21 Participants
Age, Continuous	15.75 years STANDARD_DEVIATION 6.3 • n=5 Participants	12.7 years STANDARD_DEVIATION 6.09 • n=7 Participants	13.04 years STANDARD_DEVIATION 4.98 • n=5 Participants	15.06 years STANDARD_DEVIATION 7.92 • n=4 Participants	14.29 years STANDARD_DEVIATION 6.64 • n=21 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants	13 Participants n=4 Participants	41 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	19 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	34 Participants n=21 Participants
Ethnicity (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	0 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants	11 Participants n=4 Participants	41 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Region of Enrollment United States	16 participants n=5 Participants	5 participants n=7 Participants	16 participants n=5 Participants	16 participants n=4 Participants	53 participants n=21 Participants

PRIMARY outcome

Timeframe: Beginning of preparative regimen through Day 28 after CD19 CAR infusion

Population: Only 15/16 subjects were analyzed in Phase 2, Arm 1 because one subject did not received CAR cell infusion and therefore could not be evaluated for response.

Participants with B cell malignancies who received preparative chemotherapy followed by CD19 CAR T-cells with \< Grade 4 cytokine release syndrome.

Outcome measures

Outcome measures
Measure	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) n=5 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=15 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.
Number of Participants Who Received Preparative Chemotherapy Followed by Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR T-cells With < Grade 4 Cytokine Release Syndrome	15 Participants	14 Participants	4 Participants	14 Participants

PRIMARY outcome

Timeframe: Apheresis through completion of CAR manufacturing process, approximately 2 weeks

Population: Per protocol, only patients treated in Phase 1 were analyzed for this outcome measure.

Participants who had T-cells collected by apheresis and subsequently had the amount of CAR T-cells manufactured as prescribed by the dose level they were enrolled in.

Outcome measures

Outcome measures
Measure	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) n=5 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.
Number of Participants in Which the Prescribed Dose of Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR T-cells Were Successfully Manufactured	0 Participants	15 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: 21 days of target date

Population: Per protocol, only participants on Phase 2, Arm 2 were analyzed for this outcome measure.

Participants who were administered intensive chemotherapy prior to Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): CD19 CAR infusion and received CAR cells within 21 days of the planned infusion date.

Outcome measures

Outcome measures
Measure	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.
Number of Participants Who Were Administered Intensive Chemotherapy Prior to Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR Infusion	16 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 28 days (+/- 4 days) after infusion of CD19 CAR T-cells

Population: Ph 1, Arm 1: BM analyzed in 13/16 subjects \& CSF in 14/16 subjects as results not available in additional subjects. Ph 2, Arm 1: 14/16 subjects analyzed as 1 not infused \& 1 developed PD. One additional subject didn't have BM/CSF results. Ph 2, Arm 2: 14/16 subjects analyzed as 2 developed PD. Two additional patients didn't have BM/CSF results.

Measure persistence of adoptively-transferred anti-CD19-CAR transduced T cells (defined by percent of CD19 CAR T-cells) in the blood and where possible the bone marrow and Cerebrospinal Fluid (CSF) of patients by flow cytometry assay.

Outcome measures

Outcome measures
Measure	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=14 Participants Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) n=5 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=14 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.
Mean Percentage Cluster of Differentiation 19 (CD19) - Chimeric Antigen-Receptor (CAR) T-Cells in Blood, Bone Marrow (BM) and Cerebrospinal Fluid (CSF) Peripheral blood	0.897 Percentage T-cells Standard Deviation 1.871	0.279 Percentage T-cells Standard Deviation 0.712	0.122 Percentage T-cells Standard Deviation 0.239	0.343 Percentage T-cells Standard Deviation 1.022
Mean Percentage Cluster of Differentiation 19 (CD19) - Chimeric Antigen-Receptor (CAR) T-Cells in Blood, Bone Marrow (BM) and Cerebrospinal Fluid (CSF) Bone marrow	0.814 Percentage T-cells Standard Deviation 1.775	0.459 Percentage T-cells Standard Deviation 0.781	0.554 Percentage T-cells Standard Deviation 0.979	0.552 Percentage T-cells Standard Deviation 1.308
Mean Percentage Cluster of Differentiation 19 (CD19) - Chimeric Antigen-Receptor (CAR) T-Cells in Blood, Bone Marrow (BM) and Cerebrospinal Fluid (CSF) Cerebrospinal fluid	14.742 Percentage T-cells Standard Deviation 16.301	3.186 Percentage T-cells Standard Deviation 5.304	1.825 Percentage T-cells Standard Deviation 2.943	7.192 Percentage T-cells Standard Deviation 16.728

SECONDARY outcome

Timeframe: Day 28 (+/- 4 days) after CD19 CAR infusion

Population: Only 15/16 subjects were analyzed in Phase 2, Arm 1 because one subject did not received CAR cell infusion and therefore could not be evaluated for response.

Complete Response (CR) was assessed by bone marrow evaluation was I defined as \<5% leukemic blasts.

Outcome measures

Outcome measures
Measure	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) n=5 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=15 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.
Number of Patients With a Complete Response (CR)	6 Participants	10 Participants	4 Participants	11 Participants

SECONDARY outcome

Timeframe: Day 28 (+/- 4 days) after CD19 CAR infusion.

Population: Only 15/16 subjects were analyzed in Phase 2, Arm 1 because one subject did not received CAR cell infusion and therefore could not be evaluated for response.

Participants with Grade 4 Cytokine Release Syndrome (CRS). CRS is defined as a clinical syndrome that may occur after cell therapy due to the release of cytokines (substances secreted by immune cells) into the body's blood stream.

Outcome measures

Outcome measures
Measure	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) n=5 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=15 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.
Number of Participants With Grade 4 Cytokine Release Syndrome (CRS)	1 Participants	2 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) n=5 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 Participants Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.
Number of Participants With Serious and Non-Serious Adverse Events	16 Participants	16 Participants	5 Participants	16 Participants

Adverse Events

Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)

Serious events: 6 serious events

Other events: 16 other events

Deaths: 10 deaths

Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)

Serious events: 2 serious events

Other events: 5 other events

Deaths: 3 deaths

Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)

Serious events: 1 serious events

Other events: 16 other events

Deaths: 5 deaths

Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)

Serious events: 5 serious events

Other events: 16 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Nirali N. Shah

National Cancer Institute

Phone: 240-760-6199

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 participants at risk Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%) n=5 participants at risk Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 participants at risk Lymphodepleting regimen of Fludarabine and Cyclophosphamide. Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.	Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%) n=16 participants at risk Intensive lymphodepleting chemotherapy, in lieu of the standard lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells. Anti-Cluster of Differentiation (CD)19- Chimeric antigen receptor (CAR): Cells extracted, followed by induction chemotherapy before CD19-CAR infusion.
Immune system disorders Cytokine release syndrome	18.8% 3/16 • Number of events 3 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	20.0% 1/5 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	25.0% 4/16 • Number of events 9 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Nervous system disorders Dysphasia	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	20.0% 1/5 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
General disorders Fever	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Nervous system disorders Headache	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Vascular disorders Hypotension	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Nervous system disorders Seizure	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	12.5% 2/16 • Number of events 2 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Cardiac disorders Sinus tachycardia	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	12.5% 2/16 • Number of events 2 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Cardiac disorders Cardiac arrest	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Cardiac disorders Cardiac disorders - Other, biventricular dilatation	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Cardiac disorders Heart failure	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Nervous system disorders Hydrocephalus	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Vascular disorders Hypertension	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 2 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Respiratory, thoracic and mediastinal disorders Hypoxia	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Cardiac disorders Left ventricular systolic dysfunction	6.2% 1/16 • Number of events 2 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Nervous system disorders Nervous system disorders - Other, L deviated gaze	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Nervous system disorders Nervous system disorders - Other, increased ventricle size	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Investigations Neutrophil count decreased	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Respiratory, thoracic and mediastinal disorders Respiratory failure	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Nervous system disorders Somnolence	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Cardiac disorders Cardiac disorders - Other, dilated cardiomyopathy	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Cardiac disorders Cardiac disorders - Other, elevated RVSP	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Cardiac disorders Cardiac disorders - Other, global systolic dysfunction	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Nervous system disorders Nervous system disorders - Other, intraventricular hemorrhage	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Nervous system disorders Nervous system disorders - Other, ventriculomegaly	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.
Nervous system disorders Nervous system disorders - Other, paraplegia	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/5 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.	0.00% 0/16 • Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.