AHSCT Combined With CAR-T Cells in the Treatment of Refractory and Relapsed Multiple Myeloma

Study Overview
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Brief Summary
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Clinical Study on the Safety and Effectiveness of Autologous Hematopoietic Stem Cell Transplantation Combined With CAR-T Cells in the Treatment of Refractory and Relapsed Multiple Myeloma

Detailed Description
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This is a prospectiv , single arm, open-label, single-center study. This study is indicated for refractory and relapsed multiple myeloma. It aims to evaluate the safety and effectiveness of autologous hematopoietic stem cell transplantation combined with BCMA CAR-T to treat refractory and relapsed multiple myeloma. The main research is completely alleviated, overall reaction rate, and recurrence rate,etc. 50 patients will be enrolled.

Official Title
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Clinical Study on the Safety and Effectiveness of Autologous Hematopoietic Stem Cell Transplantation Combined With CAR-T Cells in the Treatment of Refractory and Relapsed Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: BCMA CAR-T cells injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1、BCMA positive accompanied by refractory/relapsed and resistance; 2、Patients with the tumor load is high and cannot be transplanted directly, before transplantation. Reduce the load through CAR-T treatment to prepare for transplantation; 3、Patient relapses after transplantation,donor lymphocyte infusion Invalid. The donor cells in the recipient body can be used or the donor cells can be collected directly.Prepare CAR-T to prevent recurrence and induce relapsing; 4、Repeated MRD (+) refractory drug resistant cases; 5、Male or female, 30-75 years old; 6、Anticipated survival time more than 12 weeks 7、Transplant subjects, regardless of their previous treatment, are eligible for inclusion after relapse； 8、Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up; 9、Those who voluntarily participate in the trial and sign the informed consent form Exclusion Criteria: 1、Patients with the history of epilepsy or other CNS disease； 2、Patients with prolonged QT interval time or severe heart disease； 3、Pregnant or breastfeeding; 4、Active infection with no cure; 5、Patients with active hepatitis B or C infection; 6、Previously treated with any genetic therapy; 7、The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; 8、Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl; 9、Those who suffer from other uncontrolled diseases are not suitable to join the study; 10、HIV infection; 11、Any situation that the researchers believe may increase the risk of patients or interfere with the test results.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Refractory and relapsed multiple myeloma | Drug: BCMA CAR-T cells injection<br>* Autologous hematopoietic stem cell transplantation combined with BCMA CAR-T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after BCMA CAR T-cells infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | 24 months after cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate | The number of response patients/the number of total patients | Up to 30 months | 
| Complete response rate(CRR) | Proportion of subjects who achieved morphological complete response (CR) and complete response with hematologic incomplete recovery (CRi) | Baseline up to 2 years after BCMA CAR T-cells infusion | 
| Overall survival (OS) | Assessment of OS at Month 6,12,18and 24 | Month 6,12,18and 24 | 
| Duration of response(DOR) | Assessment of OS at Month 6,12,18and 24 | Month 6,12,18and 24 | 
| Progression-free survival (PFS) | Assessment of PFS at Month 6,12,18and 24 | Month 6,12,18and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AHSCT, BCMA CAR-T