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

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

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.

Study Overview

• Status: Terminated
• Conditions: Leukemia, Acute Lymphoblastic
• Intervention / Treatment: Biological: CART 19

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • UNIVERSITY of PENNSYLVANIA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CART19; CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Noelle Frey, MD, UNIVERSITY of PENNSYLVANIA

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): December 12, 2018
• Study Completion (Actual): December 12, 2018

Study Registration Dates

• First Submitted: October 12, 2016
• First Submitted That Met QC Criteria: October 13, 2016
• First Posted (Estimated): October 17, 2016

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplastic Processes; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual
• Other Study ID Numbers: UPCC39416, 825668