This phase I trial studies the side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy and NKTR-255, and to see how well they work in treating patients 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 diffuse large B-cell lymphoma and B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, 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. NKTR-255 is an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer. Giving CD19/CD22-CAR T cells and chemotherapy in combination with NKTR-255 may work better in treating patients with diffuse large B-cell lymphoma or B acute lymphoblastic leukemia.
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 adults with B cell hematologic malignancies following a cyclophosphamide/fludarabine conditioning regimen. III. Assess the safety and feasibility of administering repeated doses of NKTR-255 intravenously after CD19/CD22-CAR T cell infusions in adults with ALL using a dose escalation design. IV. Determine the recommended phase 2 dose (RP2D) of NKTR-255 when administered following CD19/CD22-CAR T cell infusion in adults with ALL SECONDARY OBJECTIVES: I. Evaluate the ability of CD19/CD22 CAR T cells to mediate clinical activity in adults with DLBCL and adults with ALL. II. Characterize the pharmacokinetics (PK) of NKTR-255 when administered post CD19/CD22 CAR T cell infusion. III. Explore the rate of relapse, progression free survival (PFS) and overall survival (OS) in subjects receiving CD19/CD22 CAR T cells, followed by up to 6 cycles of NKTR-255
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
56
Given CD19/CD22 CAR T cells IV
Given IV
Given IV
Correlative studies
Ancillary studies
Given IV
Stanford University, School of Medicine
Palo Alto, California, United States
Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/CD22 chimeric antigen receptor (CAR) T cells
Safety data will be analyzed per standard methods and interpreted descriptively for each dose cohort. Safety data will be summarized for each dose cohort separately and for all dose cohorts combined. Adverse events will be assessed using the CTCAE version 4.03 for type and severity of event. Serious Adverse Events will be summarized for each dose cohort and for all dose cohorts combined. Reasons for discontinuation of study therapy will be tabulated.
Time frame: Up to 28 days
Maximum tolerated dose of CD19/CD22 chimeric antigen receptor (CAR) T cells defined as the dose level immediately below the level at which the enrollment is stopped due to a dose limiting toxicity
Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time frame: Up to 28 days
Rate of successful manufacture and expansion of the CD19/CD22 chimeric antigen receptor (CAR) T cells to satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis
In addition to aiming to evaluate up to 6 subjects at a given dose level with respect to toxicity, the number of subjects which can successfully manufacture the targeted dose number will be determined.
Time frame: Up to 15 years
Overall survival
Will be assessed by dose cohort.
Time frame: From the start of the preparative regimen until death, assessed for up to 15 years
Progression free survival
Will be assessed by dose cohort.
Time frame: From the start of the preparative regimen until the documentation of disease progression or death due to any cause, whichever occurs first, assessed for up to 15 years
The ability to achieve a clinical response after administration of CD19/CD22 chimeric antigen receptor (CAR) T cells
Will be assessed by the Response Criteria for Lymphoma and the Response Criteria for Acute Lymphoblastic Leukemia.
Time frame: Up to 15 years
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