Autologous CD19/CD22 Chimeric Antigen Receptor T-cells in Treating Patients with Recurrent or Refractory CD19 Positive B Acute Lymphoblastic Leukemia

Active:	No
Cancer Type:	Hematopoietic Malignancies Leukemia Unknown Primary	NCT ID:	NCT03233854
Trial Phases:	Phase I	Protocol IDs:	CCT5001 (primary) NCI-2017-01291
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Stanford Cancer Institute Palo Alto
NCI Full Details:	http://clinicaltrials.gov/show/NCT03233854

Summary

This phase I trial studies the side effects of autologous CD19/CD22 chimeric antigen receptor T-cells and to see how well it works in treating patients with CD19 positive B acute lymphoblastic leukemia that has come back (recurrent) or does not respond to treatment (refractory). 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. Giving autologous CD19/CD22 chimeric antigen receptor T-cells may help treat patients with B acute lymphoblastic leukemia.

Objectives

PRIMARY OBJECTIVES:
I. Determine the feasibility of producing autologous CD19/CD22 chimeric antigen receptor T-cells (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 adults with hematologic malignancies following a cyclophosphamide/fludarabine phosphate (fludarabine) conditioning regimen.

SECONDARY OBJECTIVE:
I. Evaluate the ability of CD19/CD22-CAR T cells to mediate clinical activity in adults with diffuse large B-Cell lymphoma (DLBCL) and/or adults with acute lymphoblastic leukemia (ALL).

EXPLORATORY OBJECTIVES:
I. Evaluate the frequency of CD22+ expression on lymphoma cells, and determine site density when possible.
II. Analyze alterations in early B cell development induced by immune pressure exerted via CD19/CD22-CAR T cells.
III. Evaluate whether subjects receiving CD19/CD22-CAR T cells relapse with loss or diminished expression of CD19 and/or CD22, when feasible.
IV. Measure persistence of CD19/CD22-CAR T cells in the blood, bone marrow and cerebrospinal fluid (CSF), and explore correlations between anti CD19/CD22-CAR T cell properties and correlations between immune responses directed toward the CD19/22-CAR T cells and CAR T cell efficacy and persistence.
V. Establish the utility of chromatin structure and epigenomic technology to characterize CAR T cell therapies.

OUTLINE: This is a dose-escalation study of autologous CD19/CD22 chimeric antigen receptor T-cells.

Patients receive cyclophosphamide intravenously (IV) over 60 minutes and fludarabine phosphate IV over 30 minutes on days -5 to -3. Patients then receive autologous CD19/CD22 chimeric antigen receptor T-cells IV over 10-30 minutes on day 0. Patients that benefited from the first dose of autologous CD19/CD22 chimeric antigen receptor T-cells, had no unacceptable side effects, and have enough cells left over may receive additional doses of autologous CD19/CD22 chimeric antigen receptor T-cells based on the number of additional cells available.

After completion of study treatment, patients are followed up daily until day 14, twice per week until day 28, at 2, 3, 6, 9, and 12 months, every 6-12 months up to year 5, and then annually for years 6-15.

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