Study of T Cells Targeting CD138/BCMA/CD19/More Antigens (CART-138/BCMA/19/More) for Chemotherapy Refractory and Relapsed Multiple Myeloma

Adults ages 18-75 with Relapsed and/or Chemotherapy Refractory Multiple Myelomas.

Design:

Participants may be screened with:

Medical history Physical exam Blood and urine tests Heart tests Bone marrow sample Multiple scans and X-rays Lymphocytes are collected by apheresis from the enrolled patient or a healthy donor. Blood is removed through a needle in an arm. 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 2 chemotherapy drugs over 5 days. Two days later, participants will get an intravenous (IV) catheter in an arm. They will get the split doses CART cells on day0, day1, day2 through the IV in 1 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 at 1, 2, 3, 6, 9 and 12 months after the infusion, then every 6 months until two years after infusion. A bone marrow sample will be taken at the 3-month visit.

Inclusion criteria

• CD138 or BCMA antigen positive multiple myeloma in patients with no available curative treatment options (such as autologous or allogeneic SCT).
• Relapsed and/or refractory multiple myeloma.
• Relapsed after prior autologous or allogenic SCT.
• Expected survival ≥ 3 months
• Creatinine < 2.0 mg/dl
• Blood coagulation function: PT and APTT < 2x normal
• Arterial blood oxygen saturation > 92%
• Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) < 3x normal
• Karnofsky scores ≥ 60 and ECOG score ≤ 2
• Adequate venous access for apheresis, and no other contraindications for leukapheresis
• Patients should not take system chemotherapy in one month and 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℃)