Clinical Trials /

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

NCT02935543

Description:

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.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: UPCC39416, 825668
  • NCT ID: NCT02935543

Conditions

  • Leukemia, Acute Lymphoblastic

Interventions

DrugSynonymsArms
CART 19CART19

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
CART19ExperimentalCART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion.
  • CART 19

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01%
Time Frame:Day 28
Safety Issue:
Description: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

Measure:Best Overall Survival (OS)
Time Frame:one year
Safety Issue:
Description: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.
Measure:Duration of Remission (DOR)
Time Frame:one year
Safety Issue:
Description: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.
Measure:Relapse Free Survival (RFS)
Time Frame:one year
Safety Issue:
Description: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.
Measure:Event Free Survival (EFS)
Time Frame:one year
Safety Issue:
Description: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)
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.
Time Frame:prior to day 1
Safety Issue:
Description: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.
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).
Time Frame:one year
Safety Issue:
Description:Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS) and macrophage activation syndrome (MAS).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:University of Pennsylvania

Last Updated

February 5, 2020