Study of T Cells Targeting CD19/BCMA (CART-19/BCMA) for High Risk Multiple Myeloma Followed With Auto-HSCT
- Conditions
- Safety and Efficacy
- Interventions
- Biological: anti-CD19 and anti-BCMA CARDrug: Immunomodulatory drugs
- Registration Number
- NCT03455972
- 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 months until disease progression. A bone marrow sample will be taken at the 3-month visit.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 15
- 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.
- 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℃).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description anti-CD19 and anti-BCMA CAR anti-CD19 and anti-BCMA CAR 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) anti-CD19 and anti-BCMA CAR Immunomodulatory drugs 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)
- Primary Outcome Measures
Name Time Method OS Minimum of 2 years after first induction Is defined as time from first induction date to time of death due to any cause
Incidence and severity of adverse events Approximately 3 years Proportion of subjects with adverse events overall and by severity grade
PFS Minimum of 2 years after first induction Is defined as time from first induction date to first documentation of PD, or death due to any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Duration of best response Minimum of 2 years According to IMWG response criteria at the end of the research.
MRD negative conversion ratio and persistence Minimum of 2 years MRD negative by flow cytometry
Proportion of subjects who achieved Complete Response (CR) Rate Minimum of 2 years Percentage of subjects who achieved CR or stringent CR according to IMWG Uniform Response Criteria for Multiple Myeloma
Pharmacokinetics - Tmax Approximately 2.5 years after first CAR infused Time to peak transgene level
Pharmacokinetics - Cmax Approximately 2.5 years after first CAR infused Maximum transgene level
Pharmacokinetics - AUC Approximately 2.5 years after first CAR infused Area under the curve of the transgene level
Duration of persistence of CAR T cells in the blood Approximately 2.5 years after first CAR infused Duration of persistence of CAR T cells in the blood
Trial Locations
- Locations (1)
First Affiliated Hospital, Soochow University
🇨🇳Suzhou, Jiangsu, China