This phase I trial studies the side effects of ribonucleic acid (RNA) chimeric antigen receptor (CAR) T-19 cells and cyclophosphamide in treating patients with Hodgkin lymphoma that has come back (recurrent) or does not respond to treatment (refractory). RNA CART-19 cells are white blood cells, called T cells, modified to identify and possibly kill cancer cells. Drugs used in chemotherapy, such as 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. It is not yet known if giving RNA CART-19 cells and cyclophosphamide will help put and keep Hodgkin lymphoma in remission.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02624258.
PRIMARY OBJECTIVES:
I. Determine manufacturing feasibility of RNA electroporated CD19 CAR-CD3zeta-4-1BB-expressing autologous T-lymphocytes (RNA CART19) cells from Hodgkin lymphoma patient apheresis products.
II. Assess the safety of RNA CART19 in Hodgkin lymphoma (HL) subjects by recording the frequency and severity of adverse events reporting, including but not limited to, estimating the frequency of cytokine release syndrome (CRS) and macrophage activation syndrome (MAS).
III. Determine persistence, trafficking and biologic effects of RNA CART19 cells.
SECONDARY OBJECTIVES:
I. Estimate the efficacy of at least 1 dose of:
Ia. Subjects < 80 kg: 8 x 10^5 - 1.5 x 10^6 RNA CART19 cells/kg/dose (maximum per dose, 1.2 x 10^8 RNA CART19 cells) or
Ib. Subjects >= 80 kg: 1 x 10^8 RNA CART19 cells/dose +/- 20% (maximum per dose, 1.2 x 10^8 RNA CART19 cells)
II. Describe the survival and response rates.
III. Evaluate impact of RNA CART19 treatment on systemic soluble immune factors in patients.
IV. Determine the effect of RNA CART19 cells on the tumor microenvironment in HL.
OUTLINE:
Patients receive cyclophosphamide intravenously (IV) on days -4 to -1. Patients then receive RNA CART19 cells IV over up to 20 minutes on days 0, 2, 4, 9, 11 and 14 (if day 0 occurs on Monday), days 0, 2, 5, 9, 12, and 14 (if day 0 occurs on Wednesday) or days 0, 3, 5, 10, 12 and 14 (if day 0 occurs on Friday), in the absence of disease progression or unacceptable toxicity. Patients may receive cyclophosphamide IV on day 7 after the first 3 RNA CART19 doses.
After completion of study treatment, patients are followed up on days 21 and 28, and at 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, and 24 months.
Lead OrganizationChildren's Hospital of Philadelphia
Principal InvestigatorSusan Robbins Rheingold
