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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

About this trial

This is an interventional treatment trial for Leukemia, Acute Lymphoblastic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:
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
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

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

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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