Safety and Efficacy
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALanti-CD19 and anti-BCMA CAR
Participants will get auto-HSCT. Hematopoietic reconstitution after auto-HSCT, participants will get the anti-CD19 CAR T cells (1×10e+7/kg on d0) and anti-BCMA CAR T cells as split-dose (total 5×10e+7/kg, 40% on d1 and 60% on d2)
DRUGImmunomodulatory drugs
Maintenance therapy
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
No
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℃).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events | Approximately 2 years | Proportion of subjects with adverse events overall and by severity grade |
| PFS, response | every 6 months after first induction | 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. |
| CAR-T Pharmacokinetics | Minimum of 2 years after first induction | Maximum transgene level, Time to peak transgene levelm, persistence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRD negative conversion ratio and persistence | every 3 months for first year, then every 6 months | MRD negativity by flow cytometry |
| lymphocyte subsets analysis | Minimum of 2 years | Proportion of sub-lymphocytes Monitoring by flow cytometry |
| immune mutation | Minimum of 2 years | Proportion of T-reg cells and B-reg cells detected whether the treatment process induces an immune response to murine single-chain antibodies in patients |
| Patients quality of life | within 1 year post CART infusion | HRQoL was assessed with the EORTC QLQ-C30 after transplantation followed by CAR-T therapy. |
Countries
China
Contacts
STUDY_CHAIRdepei wu
The First Affiliated Hospital of Soochow University
Outcome results
None listed