CART19 in Adult Patients With Minimal Residual Disease During Upfront Treatment for ALL
Primary Purpose
Leukemia, Acute Lymphoblastic
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CART 19
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Acute Lymphoblastic
Eligibility Criteria
Inclusion Criteria:
- Patients with CD19+, B cell Acute Lymphoblastic Leukemia (B-ALL) who have 0.01%≤MRD<10% during upfront treatment
- Patients must be within 18 months of initial ALL diagnosis
- Age ≥18 years
Adequate organ function defined as:
- Creatinine ≤ grade 2
- ALT/AST ≤3x upper limit of normal range for age
- Direct bilirubin ≤2.0 mg/dl
- Adequate pulmonary function defined as ≤ grade 2 dyspnea and ≤ grade 2 hypoxia
- Cardiac Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
- Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy.
- Expression of CD19 on leukemic blasts demonstrated by flow cytometry or immunohistochemistry of bone marrow or peripheral blood
- Adequate performance status defined as ECOG Performance Status 0 or 1
- Provides written informed consent
- Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol
Exclusion Criteria:
- Active, uncontrolled infection
- Active hepatitis B or hepatitis C
- HIV Infection
- Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 2)
- Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of enrollment.
- Pregnant or nursing (lactating) women
- 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.
Sites / Locations
- University of Pennsylvania
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CART19
Arm Description
CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
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.
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.
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)
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.
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).
Full Information
NCT ID
NCT02935543
First Posted
October 12, 2016
Last Updated
June 20, 2023
Sponsor
University of Pennsylvania
1. Study Identification
Unique Protocol Identification Number
NCT02935543
Brief Title
CART19 in Adult Patients With Minimal Residual Disease During Upfront Treatment for ALL
Official Title
Phase 2 Study of CD19-directed Chimeric Antigen Receptor-modified T Cells (CART19) for Adult Patients With Minimal Residual Disease During Upfront Treatment for Acute Lymphoblastic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Why Stopped
Study is terminated because of administrative reasons.
Study Start Date
October 2016 (Actual)
Primary Completion Date
December 12, 2018 (Actual)
Study Completion Date
December 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Acute Lymphoblastic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CART19
Arm Type
Experimental
Arm Description
CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion.
Intervention Type
Biological
Intervention Name(s)
CART 19
Intervention Description
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
Primary Outcome Measure Information:
Title
The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01%
Description
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
Secondary Outcome Measure Information:
Title
Best Overall Survival (OS)
Description
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
Title
Duration of Remission (DOR)
Description
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
Title
Relapse Free Survival (RFS)
Description
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
Title
Event Free Survival (EFS)
Description
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
Title
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.
Description
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
Title
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).
Description
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS) and macrophage activation syndrome (MAS).
Time Frame
one year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with CD19+, B cell Acute Lymphoblastic Leukemia (B-ALL) who have 0.01%≤MRD<10% during upfront treatment
Patients must be within 18 months of initial ALL diagnosis
Age ≥18 years
Adequate organ function defined as:
Creatinine ≤ grade 2
ALT/AST ≤3x upper limit of normal range for age
Direct bilirubin ≤2.0 mg/dl
Adequate pulmonary function defined as ≤ grade 2 dyspnea and ≤ grade 2 hypoxia
Cardiac Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy.
Expression of CD19 on leukemic blasts demonstrated by flow cytometry or immunohistochemistry of bone marrow or peripheral blood
Adequate performance status defined as ECOG Performance Status 0 or 1
Provides written informed consent
Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol
Exclusion Criteria:
Active, uncontrolled infection
Active hepatitis B or hepatitis C
HIV Infection
Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 2)
Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of enrollment.
Pregnant or nursing (lactating) women
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Noelle Frey, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
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CART19 in Adult Patients With Minimal Residual Disease During Upfront Treatment for ALL
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