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

Phase 2

Terminated

• Conditions: Leukemia, Acute Lymphoblastic
• Interventions: Biological: CART 19

• Registration Number: NCT02935543
• Lead Sponsor: University of Pennsylvania

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-10
• Study First Submitted: 2016-10-12
• Study First Submitted QC: 2016-10-13
• Study First Posted: 2016-10-17
• Primary Completion: 2018-12-12
• Study Completion: 2018-12-12
• Status Verified: 2020-01
• Results First Submitted: 2020-01-09
• Results First Submitted QC: 2020-01-27
• Results First Posted: 2020-02-05
• Last Update Submitted: 2023-06-20
• Last Update Posted: 2023-06-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CART19	CART 19	CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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).
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.
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.
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)

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States