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

• ClinicalTrials.gov Identifier: NCT02935543
• Recruitment Status: Terminated
• First Posted: October 17, 2016
• Results First Posted: February 5, 2020
• Last Update Posted: February 5, 2020
• Sponsor: University of Pennsylvania
• Information provided by (Responsible Party): University of Pennsylvania

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.

Condition or disease	Intervention/treatment	Phase
Leukemia, Acute Lymphoblastic	Biological: CART 19	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 2016
• Actual Primary Completion Date: December 12, 2018
• Actual Study Completion Date: December 12, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01% [ Time Frame: 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 :

1. Best Overall Survival (OS) [ Time Frame: 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.
2. Duration of Remission (DOR) [ Time Frame: 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.
3. Relapse Free Survival (RFS) [ Time Frame: 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.
4. Event Free Survival (EFS) [ Time Frame: 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)
5. 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 ]
   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.
6. 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). [ Time Frame: one year ]
   Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS) and macrophage activation syndrome (MAS).

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

University of Pennsylvania

Investigators

• Principal Investigator: Noelle Frey, MD; University of Pennsylvania

  Study Documents (Full-Text)

Documents provided by University of Pennsylvania:

Study Protocol and Statistical Analysis Plan  [PDF] March 15, 2017

More Information

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02935543
• Other Study ID Numbers: UPCC39416, 825668
• First Posted: October 17, 2016
• Results First Posted: February 5, 2020
• Last Update Posted: February 5, 2020
• Last Verified: January 2020

Additional relevant MeSH terms:

Leukemia; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases