Autologous Hematopoietic Stem Cell Transplantation Combined With CAR-T Cells in the Treatment of Refractory and Relapsed Malignant Lymphoma

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 Malignant Lymphoma

Detailed Description
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Current studies have shown that under standard treatment, patients with large masses and high-grade DLBCL have a poor prognosis. Data from major centers around the world on CAR-T cell treatment of relapsed and refractory B-cell NHL show that CAR-T treatment of relapsed and refractory B-cell NHL has a low complete remission rate but a low recurrence rate after remission.Therefore, new treatment options are urgently needed to achieve long-term relief. CD19 CAR-T therapy as a consolidation therapy after high-dose melphalan and autologous hematopoietic stem cell transplantation has been used in a refractory MM patient at the University of Pennsylvania, and good research progress has been made. Craig S et al. studied the safety and effectiveness of CD19 CAR-T cell therapy after high-dose chemotherapy and autologous stem cell transplantation HDT-ASCT. The object of the study was relapsed and refractory non-Hodgkin's lymphoma, with 2-year progression-free survival ( PFS) is 30%. Therefore, autologous hematopoietic stem cell transplantation combined with CAR-T cell therapy is expected to improve the complete remission rate and long-term survival rate. In summary, the center intends to apply for a clinical trial of autologous hematopoietic stem cell transplantation combined with CAR-T cells for the treatment of refractory and relapsed non-Hodgkin's lymphoma.

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 Malignant Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: Autologous hematopoietic stem cell transplantation combined with CD19 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Male or female, 18-75 years old (including the threshold value); 2. According to the 2016 WHO classification criteria for lymphocytic tumors, histologically confirmed include: DLBCL (NOS); follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma transformed DLBCL, and PMBCL and high-grade B-cell lymphoma Subject. 3.R/R B-NHL (conform one of the following conditions) The subject did not remission or relapsed after receiving second-line or higher-line chemotherapy Primary resistance The subject relapsed after receiving autologous hematopoietic stem cell transplantation Exclusion Criteria: Subjects with any of the following exclusion criteria were not eligible for this trial: History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases; Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; Pregnant (or lactating) women; Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); Active infection of hepatitis B virus or hepatitis C virus; Those who have used any gene therapy products before. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl; Those who suffer from other uncontrolled diseases are not suitable to join the study; HIV infection; 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: 18 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 of Lymphoma<br>Refractory and relapsed malignant lymphoma | Biological: Autologous hematopoietic stem cell transplantation combined with CD19 CAR-T cells<br>* The patient receives ECHOP chemotherapy or other chemotherapy regimens； G-CSF in the low cell stage mobilizes hematopoietic stem cells and freezes them for later use after collection； Autologous hematopoietic stem cells and prepared CD19 CAR-T cells are reinfused into the patient<br>|

What is the study measuring?
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Primary 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 | 
| 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(ORR) | Assessment of ORR (ORR = CR + CRi ) at Month 1,3,6,12,18and 24 | Month 1,3,6,12,18and 24 | 
| Progression-free survival (PFS) | Assessment of PFS at Month 6,12,18and 24 | Month 6,12,18and 24 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASCT, CD19 CAR-T