Clinical trial NCT02935543: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia, Acute Lymphoblastic
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2016-10-17
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01%
timeFrame: Day 28
Secondary outcomes:
measure: Best Overall Survival (OS)
timeFrame: one year
measure: Duration of Remission (DOR)
timeFrame: one year
measure: Relapse Free Survival (RFS)
timeFrame: one year
measure: Event Free Survival (EFS)
timeFrame: one year
measure: 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.
timeFrame: prior to day 1
measure: 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).
timeFrame: one year
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Noelle Frey, MD
role: PRINCIPAL_INVESTIGATOR
References: