Study of T Cells Targeting CD19/BCMA (CART-19/BCMA) for High Risk Multiple Myeloma Followed With Auto-HSCT

Adults ages 18-75 with high risk Multiple Myelomas (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).

Design:

Participants may be screened with:

Medical history Physical exam Blood and urine tests Heart tests Bone marrow sample Multiple scans and X-rays Participants will have apheresis. Blood is removed through a needle in an arm. T cells are removed. The rest of the blood is returned through a needle in the other arm.

The cells will be changed in a laboratory. Participants will get auto-HSCT. Hematopoietic reconstitution after auto-HSCT, participants will get the T cells through the IV within 3 days. Maintenance therapy with IMiDs was received after combined CAR T infusion.

After this, participants will stay in the hospital for at least 9 days and stay nearby for 2 weeks. Then they will have blood tests and see a doctor.

Participants will visit the clinic 1, 2, 3, 6, 9 and 12 months after the infusion, then every 3-6 months until disease progression. A bone marrow sample will be taken at the 3-6 months visit.

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℃).