Multiple Myeloma
Conditions
Brief summary
Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells. Genetically engineered lymphocyte (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 multiple myeloma.To test the safety and efficacy of giving targeting CD138 or B-cell maturation antigen or CD19 or more antigens T cells in treating patients with multiple myeloma that is refractory to further chemotherapy or relapsed(after stem cell transplantation or intensive chemotherapy).
Detailed description
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.
Interventions
BIOLOGICALCART-138/BCMA/19/more
Cyclophosphamide，Fludarabine，CART-138/BCMA /19/more cells Cyclophosphamide: 300 mg/m2 IV over 30 minutes on days -5 , -4,and -3; Fludarabine: 30 mg/m2 IV over 30 minutes immediately following the cyclophosphamide on day -5, -4, and -3 Biological: Anti-CD138/BCMA/CD19/more total CART cells 5x106- 100x106 CAR+ T cells per kg of recipient bodyweight
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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℃)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine if there is grade 3 to 5 cytokine release syndrome | 2 weeks-12 months after initial dose | Number of Patients With Grade 3 Through Grade 5 Cytokine Release Syndrome(CRS) That Are Related to Study Intervening Measures, Graded According to NCI CTCAE Version 4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigators try to assess major reaction rate (MRR, PR+VGPR+CR) at the end of the research. | up to 24 weeks | Number of Patients achieved major reaction rate (MRR;PR+VGPR+CR) According to IMWG response criteria at the end of the research. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Investigators try to test CART 138 cells copies in vivo. | 2 years | CART Cell survival time by testing CART-138/BCMA cells copies in vivo through PCR Method. |
Countries
China
Contacts
Primary ContactLing zhi Yan, PhD
Outcome results
None listed