CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* City of Hope (COH) pathology review confirms that research participant's diagnostic material is consistent with history of intermediate grade B-cell NHL (e.g., diffuse B-cell lymphoma, mantle cell lymphoma, transformed follicular lymphoma)
* History of relapse after achieving first remission with primary therapy, or failure to achieve remission with primary therapy
* Life expectancy \> 16 weeks
* Karnofsky performance scale (KPS) \>= 70%
* Negative serum pregnancy test for women of childbearing potential
* Research participant has an indication to be considered for autologous stem cell transplantation

Exclusion Criteria:

* Fails to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I/II study; evidence of understanding includes passing the Protocol Comprehensive Screening given by the Research Subject Advocate (RSA); a legal guardian may substitute for the research participant
* Any standard contraindications to myeloablative HSCT per standard of care practices at COH
* Dependence on corticosteroids
* Currently enrolled in another investigational therapy protocol
* Human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of enrollment
* History of allogeneic HSCT or prior autologous HSCT
* Active autoimmune disease requiring systemic immunosuppressive therapy
* Research participant(s) who are to receive radioimmunotherapy (Zevalin-based)-based conditioning regimens
* Research participant(s) with known active hepatitis B or C infection

主要终点：Number of Participants With Dose Limiting Toxicities (DLTs) · Number of DLTs per dose level are reported. A DLT is defined as: Any grade 3 or higher toxicity, with the exception of expected adverse events; and designated as definitely or probably related (level of attribution) to the infusion of the TCM cells; and occurring within 28 days of T-cell infusion; Any toxicity requiring the use of steroids to ablate side effects attributable to the infusion of the TCM cells, and occurring within 28 days of T-cell infusion; Any toxicity which is a lower grade, but that increases in grade to a grade 3 or higher as a direct result of the TCM, and occurring within 28 days of T-cell infusion; Any grade 2 or greater autoimmune toxicity, and occurring within 28 days of T-cell infusion. · Within 28 days of T-cell infusion；Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) Detection Above Background · Peak expansion of WPRE is expressed in CAR copy number/mL of blood is summarized with median and range · 28 days post T cell infusion；Number of Days of Quantifiable CD19 CAR Post T-cell Infusion · WPRE persistence of quantifiable CD19 CAR summarized with mean and standard deviation · 28 days post T cell infusion
次要终点：Failure to Engraft；Progression-free Survival at 1 Year

• Treatment (cellular adoptive immunotherapy following PBSCT) · EXPERIMENTAL · Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with G-CSF and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplant. Patients receive standard myeloablative conditioning followed by autologous PBSCT. Patients then undergo infusion of ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR on day 2 or 3 after transplant.

This phase I/II trial studies the side effects and best dose of genetically engineered lymphocyte therapy and to see how well it works after peripheral blood stem cell transplant (PBSCT) in treating patients with high-risk, intermediate-grade, B-cell non-Hodgkin lymphoma (NHL). Genetically engineered lymphocyte therapy may stimulate the immune system in different ways and stop cancer cells from growing. Giving rituximab together with chemotherapy before a PBSCT stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim (G-CSF), or plerixafor helps stem cells move from the bone marrow to the blood so they can be collected and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving genetically engineered lymphocyte therapy after PBSCT may be an effective treatment for NHL.