Phase I Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies

Recurrent Adult Acute Lymphoblastic Leukemia Clinical Trial

Official title: Phase I Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies

Status Recruiting

Clinical Trial Summary

This phase I trial studies the best dose and side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy, and to see how well they work in treating children or young adults with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CD19/CD22-CAR T cells and chemotherapy may work better in treating children or young adults with B acute lymphoblastic leukemia.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Determine the feasibility of producing CD19/CD22-CAR T cells meeting the established release criteria.

II.Assess the safety of administering escalating doses of autologous CD19/CD22-CAR T cells that meet established release specifications in children and young adults with B-cell hematologic malignancies following a cyclophosphamide/fludarabine conditioning regimen. The following dose escalation will be used in two disease groups: 1) children and young adults with relapsed/refractory low disease burden ALL (< 5% blasts), and 2) children and young adults with relapsed/refractory high disease burden ALL (≥5% blasts) or lymphoma:

1. Dose Level -1: 3 x 105 transduced T cells/kg (± 20%)

2. Dose Level 1: 1 x 106 transduced T cells/kg (± 20%)

3. Dose Level 2: 3 x 106 transduced T cells/kg (± 20%)

4. Dose Level 3: 1 x 107 transduced T cells/kg (± 20%)

SECONDARY OBJECTIVES:

I. Evaluate the ability of CD19/CD22-CAR T cells to mediate clinical activity in children and young adults with B-acute lymphoblastic leukemia (ALL).

TERTIARY OBJECTIVES:

I. Analyze alterations in early B cell development induced by immune pressure exerted via CD19/CD22-CAR T cells.

II. Evaluate whether subjects receiving CD19/CD22-CAR T cells relapse with loss or diminished expression of CD19 and/or CD22, when feasible.

III. Measure persistence of CD19/CD22-CAR T cells in the blood, bone marrow and cerebral spinal fluid (CSF), and explore correlations between CD19/CD22-CAR T cell properties and CAR T cell efficacy and persistence.

IV. Establish the utility of chromatin structure and epigenomic technology to characterize CAR T cell therapies.

V. Explore the ability of CD19/CD22-CAR T cells to mediate clinical activity in children and young adults with refractory B cell lymphoma in a non-statistical cohort due to expectations of low accrual.

OUTLINE: This is a dose-escalation study of CD19/CD22-CAR T cells.

Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2 and cyclophosphamide IV over 60 minutes on day -2. Patients then receive CD19/CD22-CAR T cells IV over 10-20 minutes on day 0. Patients that benefited from the first dose of CD19/CD22-CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22-CAR T cells.

After completion of study treatment, patients are followed up daily until day 14, twice weekly until day 28, at 2 and 3 months, every 3 months until month 12, every 6-12 months up to year 5, and then annually for years 6-15. ;

Related Conditions & MeSH terms

• B Acute Lymphoblastic Leukemia
• CD19 Positive
• Leukemia
• Leukemia, Lymphoid
• Minimal Residual Disease
• Neoplasm, Residual
• Philadelphia Chromosome
• Philadelphia Chromosome Positive
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrence
• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Refractory Acute Lymphoblastic Leukemia

• NCT number: NCT03241940
• Study type: Interventional
• Source: Stanford University
• Contact: Michelle Fujimoto
• Phone: 650-736-0539
• Email: mfujimoto@stanford.edu
• Status: Recruiting
• Phase: Phase 1
• Start date: October 20, 2017
• Completion date: August 1, 2035