CD19-Specific T-cells in Treating Patients With Advanced Lymphoid Malignancies
Condition: Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia; Blasts 5 Percent or More of Bone Marrow Nucleated Cells; CD19 Positive; Minimal Residual Disease; Non-Hodgkin Lymphoma; Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasm, Residual; Leukemia, Biphenotypic, Acute
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I clinical trial studies the side effects and best dose of CD19-specific T-cells
      in treating patients with lymphoid malignancies that have spread to other places in the body
      and usually cannot be cured or controlled with treatment. Sometimes researchers change the
      deoxyribonucleic acid (DNA) (genetic material in cells) of donated T-cells (white blood cells
      that support the immune system) using a process called "gene transfer." Gene transfer
      involves drawing blood from the patient, and then separating out the T-cells using a machine.
      Researchers then perform a gene transfer to change the T-cells' DNA, and then inject the
      changed T-cells into the body of the patient. Injecting modified T-cells made from the
      patient may help attack cancer cells in patients with advanced B-cell lymphoma or leukemia.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the safety and maximum tolerated dose of genetically modified, CD19-specific
      T cells administered into patients with CD19+ advanced lymphoid malignancies.

      SECONDARY OBJECTIVES:

      I. To screen for the development of host immune responses against the CD19-specific chimeric
      antigen receptor (CAR).

      II. To describe the homing ability of the infused T cells. III. To assess disease response.
      IV. To determine persistence of CAR+ T cells.

      OUTLINE: This is a dose escalation study of CD19 positive chimeric antigen receptor T-cells.

      LYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of
      fludarabine phosphate intravenously (IV) over 1 hour and cyclophosphamide IV over 3 hours on
      days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the
      treating physician.

      Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric
      antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0
      and 1.

      After completion of study treatment, patients are followed up for at least 15 years.
    

Intervention name(s): Cyclophosphamide; Fludarabine Phosphate; Laboratory Biomarker Analysis; Tisagenlecleucel
Intervention type(s): Drug; Drug; Other; Biological
Intervention description(s): Given IV; Given IV; Correlative studies; Given IV
Other intervention name(s): (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; SH T 586; CART-19; CART19; CTL019; CTL019 T-cells; Kymriah; Tisagenlecleucel-T
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Tisagenlecleucel
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment