Trial Outcomes & Findings for T Cells Expressing Fully-human Anti-CD19 and Anti-CD20 Chimeric Antigen Receptors for Treating B-cell Malignancies and Hodgkin Lymphoma (NCT NCT04160195)

Last Updated: 2022-02-15

Results Overview

A DLT are defined as toxicities assessed by the Common Terminology Criteria for Adverse Events v5.0 that are possibly, probably, or definitely attributable to protocol interventions and occurring between the first protocol treatment through 28 days after the CAR T-cell infusion.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

2 participants

Primary outcome timeframe

First protocol treatment through 28 days after the CAR T-cell infusion.

Results posted on

2022-02-15

Participant Flow

Participant milestones

Participant milestones
Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Overall Study STARTED	2	0
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Overall Study Principal investigator stopped study due to instability of chimeric antigen receptor gene.	1	0

Baseline Characteristics

T Cells Expressing Fully-human Anti-CD19 and Anti-CD20 Chimeric Antigen Receptors for Treating B-cell Malignancies and Hodgkin Lymphoma

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: First protocol treatment through 28 days after the CAR T-cell infusion.

Population: 1/2 participants were evaluable on group 1 and no participants were enrolled on group 2. The study was terminated. No participants experienced a DLT probably or definitely attributable to interventions.

Outcome measures

Outcome measures
Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation n=1 Participants All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Number of Participants Administered T Cells Expressing a Novel Fully- Human Anti-cluster of Differentiation 19 (CD19) and Anti-cluster of Differentiation 20 (CD20) Chimeric Antigen Receptors (CAR) Who Experienced a Dose-limiting Toxicity (DLT) Peripheral Motor Neuropathy Possibly Related	1 Participants	0 Participants
Number of Participants Administered T Cells Expressing a Novel Fully- Human Anti-cluster of Differentiation 19 (CD19) and Anti-cluster of Differentiation 20 (CD20) Chimeric Antigen Receptors (CAR) Who Experienced a Dose-limiting Toxicity (DLT) Guillain-Barre Syndrome Possibly Related	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 119 days after CAR T-cell infusion

Population: 1/2 participants were treated on group 1 and no participants were enrolled on group 2. The study was terminated.

We measured CAR T-cell persistence by detecting the CAR gene in peripheral blood mononuclear cells (PBMC) by polymerase chain reaction (PCR).

Outcome measures

Outcome measures
Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation n=1 Participants All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Percentage of Peak Blood Chimeric Antigen Receptors (CAR) T Cells	10.5 percentage of PBMC	—

SECONDARY outcome

Timeframe: pretreatment and multiple days from day 1 to day 173 after infusion.

Population: 1/2 participants were treated on group 1 and no participants were enrolled on group 2. The study was terminated.

Peak blood levels of Chimeric Antigen Receptors (CAR) T cells were measured by exact Wilcoxon rank sum test.

Outcome measures

Outcome measures
Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation n=1 Participants All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Percentage of Peripheral Blood Mononuclear Cells (PBMC) of Chimeric Antigen Receptors (CAR) T Cells	10.47 percentage of PBMC	—

SECONDARY outcome

Timeframe: Approximately 1 year 5 months

Population: 1/2 participants were evaluable on group 1 and no participants were enrolled on group 2 because the study was terminated.

Response for lymphoma was assessed by the Revised Response Criteria for Malignant Lymphoma and The Lugano Classification. Complete Remission (CR) is complete disappearance of all detectable clinical evidence of disease. Partial Remission (PR) is ≥ 50% decrease in nodes or masses. Progressive Disease (PD) is Response ≥ 50% increase in a single node. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor PD. For participants with Chronic Lymphocytic Leukemia (CLL),response was assessed by the International Workshop on CLL. CR is no lymph nodes ≥ 1.5 cm on physical exam or relevant computed tomography. PR is a ≥ 50% decrease in peripheral B lymphocyte count from pre-treatment value. PD is a ≥ 50% increase in the greatest diameter of any lymph node that was enlarged pretreatment. And SD are participants who do not fulfill the criteria for CR, PR or PD.

Outcome measures

Outcome measures
Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation n=1 Participants All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Number of Participants With Clinical Response Complete Remission	0 Participants	—
Number of Participants With Clinical Response Partial Remission	1 Participants	—
Number of Participants With Clinical Response Progressive Disease	0 Participants	—
Number of Participants With Clinical Response Stable Disease	0 Participants	—

SECONDARY outcome

Timeframe: 119 days after CAR T-cell infusion

Population: 1/2 participants were treated on group 1 and no participants were enrolled on group 2. The study was terminated.

Chimeric Antigen Receptors (CAR) T cell persistence was measured in the blood by quantitative polymerase chain reaction (PCR). CAR T cells that are detected in the participant's blood that persist for a significant length of time is a positive finding.

Outcome measures

Outcome measures
Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation n=1 Participants All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Last Time-Point at Which Chimeric Antigen Receptors (CAR) T Cells Were Detected in the Blood	119 Days	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 7 months and 18 days.

Population: 1/2 participants were treated on group 1 and no participants were enrolled on group 2. The study was terminated.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation n=1 Participants All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: First protocol treatment through 28 days after the CAR T-cell infusion.

The maximum tolerated dose is the dose at which a maximum of 1 of 6 participants has a dose-limiting toxicity (DLT). A DLT are defined as toxicities that are possibly, probably, or definitely attributable to protocol interventions and occurring between the first protocol treatment through 28 days after the CAR T-cell infusion.

Outcome measures

Outcome measures
Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation n=1 Participants All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Maximum Tolerated Dose (MTD) of Chimeric Antigen Receptors (CAR) T Cells	NA T cells The MTD was not found because 1/2 participants were treated on group 1 and no participants were enrolled on group 2. The study was terminated.	—

Adverse Events

1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation n=1 participants at risk All patients will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Gastrointestinal disorders Dysphagia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Nervous system disorders Peripheral motor neuropathy	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Nervous system disorders Peripheral sensory neuropathy	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Nervous system disorders Tremor	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.

Other adverse events

Additional Information

Dr. James N. Kochenderfer

National Cancer Institute

Phone: 240-760-6062

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation n=2 Participants All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	Total n=2 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	—	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Age, Continuous	54.95 years STANDARD_DEVIATION 12.52 • n=5 Participants	—	54.95 years STANDARD_DEVIATION 12.52 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	—	2 participants n=5 Participants

Measure	1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation n=1 participants at risk All patients will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3	2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells: Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0 Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 Fludarabine: 30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Investigations Alanine aminotransferase increased	100.0% 1/1 • Number of events 3 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Blood and lymphatic system disorders Anemia	100.0% 1/1 • Number of events 13 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Metabolism and nutrition disorders Anorexia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Investigations Aspartate aminotransferase increased	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
General disorders Fatigue	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
General disorders Fever	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Nervous system disorders Headache	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Vascular disorders Hypertension	100.0% 1/1 • Number of events 3 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 1/1 • Number of events 6 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Metabolism and nutrition disorders Hypokalemia	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Metabolism and nutrition disorders Hyponatremia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Metabolism and nutrition disorders Hypophosphatemia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Infections and infestations Lung infection	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Investigations Lymphocyte count decreased	100.0% 1/1 • Number of events 16 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Investigations Lymphocyte count increased	100.0% 1/1 • Number of events 5 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Investigations Neutrophil count decreased	100.0% 1/1 • Number of events 6 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
General disorders Pain	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Nervous system disorders Peripheral motor neuropathy	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Skin and subcutaneous tissue disorders Rash maculo-papular	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Respiratory, thoracic and mediastinal disorders Voice alteration	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.
Investigations White blood cell decreased	100.0% 1/1 • Number of events 8 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.	— 0/0 • Date treatment consent signed to date off study, approximately 7 months and 18 days. No participants were enrolled on group 2 because the study was stopped. The chimeric antigen receptor (CAR) gene used in this study is prone to recombination events and is therefore not stable. And 1/2 participants were treated on group 1.