CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Multiple myeloma patients eligible for auto-HSCT.
* High risk multiple myeloma (R-ISS III stage or with extramedullary infiltration or with del(17p), t(4;14), t(14;16), t(14;20), 1q21+ or disease progression during treatment).
* Expected survival ≥ 3 months.
* Creatinine \< 2.0 mg/dl.
* Blood coagulation function: PT and APTT \<2x normal.
* Arterial blood oxygen saturation\>92%.
* ALT(alanine aminotransferase)/AST (aspartate aminotransferase)\< 3x normal
* Karnofsky scores ≥ 60 and ECOG score≤2.
* Adequate venous access for apheresis, and no other contraindications for leukapheresis.
* Patients should not take immunotherapy in three months prior to CART cells infusion.
* Voluntary informed consent is given.

Exclusion Criteria:

* Pregnant or lactating women.
* Uncontrolled active infection.
* Active hepatitis B or hepatitis C infection.
* Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
* Previously treatment with any gene therapy products.
* Any uncontrolled active medical disorder that would preclude participation as outlined.
* HIV infection.
* History of myocardial infarction and severe arrhythmia in half a year.
* Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
* Patients with fever of unknown origin (T\>38℃).

主要终点：Incidence and severity of adverse events · Proportion of subjects with adverse events overall and by severity grade · Approximately 2 years；PFS, response · mPFS of all patients. PFS is defined as time from first induction date to first documentation of PD, or death due to any cause, whichever occurs first. Percentage of patients with sCR. Response was graded according to IMWG response criteria. · every 6 months after first induction；CAR-T Pharmacokinetics · Maximum transgene level, Time to peak transgene levelm, persistence · Minimum of 2 years after first induction
次要终点：MRD negative conversion ratio and persistence；lymphocyte subsets analysis；immune mutation；Patients quality of life

• anti-CD19 and anti-BCMA CAR · EXPERIMENTAL · Participants will get auto-HSCT. Hematopoietic reconstitution after auto-HSCT, participants will get the anti-CD19 CAR T cells (on d0) and anti-BCMA CAR T cells as split-dose (40% on d1 and 60% on d2)

CART therapy has showed good safety and efficacy in treatment of lymphoma and acute lymphoblastic leukemia. Researchers want to see if this helps people with high risk multiple myeloma after auto-HSCT.To test the safety and efficacy of giving targeting CD19 and BCMA T cells in treating high risk multiple myeloma followed with auto-HSCT.