CART19 in Adult Patients With Minimal Residual Disease During Upfront Treatment for ALL

Leukemia, Acute Lymphoblastic Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02935543
• Other study ID #: UPCC39416, 825668
• Status: Terminated
• Phase: Phase 2
• Start date: October 2016
• Est. completion date: December 12, 2018

Study information

• Verified date: January 2020
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 12, 2018
• Est. primary completion date: December 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Acute Lymphoblastic
• Neoplasm, Residual
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• 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

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Day 28
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.	one year
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.	one year
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.	one year
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)	one year
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.	prior to day 1
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).	one year