Leukemia, Acute Lymphoblastic
Conditions
Brief summary
This is a single center, single arm, open-label phase 2 study to determine the efficacy of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as CART19 cells) in adults with minimal residual disease (MRD) during upfront treatment for CD19+ acute lymphoblastic leukemia.
Interventions
BIOLOGICALCART 19
CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion. Subjects will receive 1-5 x 10\^8 transduced CAR T cells as a split dose over three days as follows:Day 1, 10% fraction: 1-5x10\^7 CART19 cells, Day 2, 30% fraction: 3x10\^7-1.5x10\^8 CART19 cells, Day 3, 60% fraction: 6x10\^7-3x10\^8 CART19 cells
Sponsors
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with CD19+, B cell Acute Lymphoblastic Leukemia (B-ALL) who have 0.01%≤MRD\<10% during upfront treatment 2. Patients must be within 18 months of initial ALL diagnosis 3. Age ≥18 years 4. Adequate organ function defined as: 1. Creatinine ≤ grade 2 2. ALT/AST ≤3x upper limit of normal range for age 3. Direct bilirubin ≤2.0 mg/dl 4. Adequate pulmonary function defined as ≤ grade 2 dyspnea and ≤ grade 2 hypoxia 5. Cardiac Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA 5. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy. 6. Expression of CD19 on leukemic blasts demonstrated by flow cytometry or immunohistochemistry of bone marrow or peripheral blood 7. Adequate performance status defined as ECOG Performance Status 0 or 1 8. Provides written informed consent 9. Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol
Exclusion criteria
1. Active, uncontrolled infection 2. Active hepatitis B or hepatitis C 3. HIV Infection 4. Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 2) 5. Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of enrollment. 6. Pregnant or nursing (lactating) women 7. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to leukemia or previous leukemia treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01% | Day 28 | The incidence of conversion of minimal residual disease (MRD) to \<0.01% after CART19 therapy in patients with MRD+ ALL during upfront treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Remission (DOR) | one year | Duration of remission (DOR) is defined as the duration from the date when the response criteria of CR or CRi is first met to the date of relapse or death due to ALL. |
| Relapse Free Survival (RFS) | one year | Relapse free survival (RFS) is defined as the duration between the date when the response criteria of CR or CRi is first met to the date of relapse or death due to any cause. |
| Best Overall Survival (OS) | one year | Overall survival (OS) is defined as the time from the date of the first CART19 infusion to the date of death due to any reason. |
| Percentage of Manufacturing Products That do Not Meet Release Criteria for Vector Transduction Efficiency, T Cell Product Purity, Viability, Sterility or Due to Tumor Contamination. | prior to day 1 | Percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility or due to tumor contamination. |
| Safety and Tolerability of CART19: Frequency and Severity of Adverse Events, Including, But Not Limited to, Cytokine Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS). | one year | Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS) and macrophage activation syndrome (MAS). |
| Event Free Survival (EFS) | one year | Event free survival (EFS) is defined as the time from start of the first CART19 infusion to the earliest of the following: Death from any cause Relapse Treatment failure: Defined as no response in the study and discontinuation from the study due to any of the following reasons: * Adverse event(s) * Abnormal laboratory value(s) * Abnormal test procedure results * New cancer therapy (excluding HSCT when performed in CR or CRi) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CART19 CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion.
CART 19: CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion. Subjects will receive 1-5 x 10\^8 transduced CAR T cells as a split dose over three days as follows:Day 1, 10% fraction: 1-5x10\^7 CART19 cells, Day 2, 30% fraction: 3x10\^7-1.5x10\^8 CART19 cells, Day 3, 60% fraction: 6x10\^7-3x10\^8 CART19 cells | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | CART19 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01%
The incidence of conversion of minimal residual disease (MRD) to \<0.01% after CART19 therapy in patients with MRD+ ALL during upfront treatment
Time frame: Day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CART19 | The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01% | 0 Participants |
Secondary
Best Overall Survival (OS)
Overall survival (OS) is defined as the time from the date of the first CART19 infusion to the date of death due to any reason.
Time frame: one year
Population: data were not collected
Secondary
Duration of Remission (DOR)
Duration of remission (DOR) is defined as the duration from the date when the response criteria of CR or CRi is first met to the date of relapse or death due to ALL.
Time frame: one year
Population: data were not collected
Secondary
Event Free Survival (EFS)
Event free survival (EFS) is defined as the time from start of the first CART19 infusion to the earliest of the following: Death from any cause Relapse Treatment failure: Defined as no response in the study and discontinuation from the study due to any of the following reasons: * Adverse event(s) * Abnormal laboratory value(s) * Abnormal test procedure results * New cancer therapy (excluding HSCT when performed in CR or CRi)
Time frame: one year
Population: data were not collected
Secondary
Percentage of Manufacturing Products That do Not Meet Release Criteria for Vector Transduction Efficiency, T Cell Product Purity, Viability, Sterility or Due to Tumor Contamination.
Percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility or due to tumor contamination.
Time frame: prior to day 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CART19 | Percentage of Manufacturing Products That do Not Meet Release Criteria for Vector Transduction Efficiency, T Cell Product Purity, Viability, Sterility or Due to Tumor Contamination. | 0 percentage of products |
Secondary
Relapse Free Survival (RFS)
Relapse free survival (RFS) is defined as the duration between the date when the response criteria of CR or CRi is first met to the date of relapse or death due to any cause.
Time frame: one year
Population: data were not collected
Secondary
Safety and Tolerability of CART19: Frequency and Severity of Adverse Events, Including, But Not Limited to, Cytokine Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS).
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS) and macrophage activation syndrome (MAS).
Time frame: one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CART19 | Safety and Tolerability of CART19: Frequency and Severity of Adverse Events, Including, But Not Limited to, Cytokine Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS). | 100 percentage of participants |