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

Early Phase 1

Recruiting

• Conditions: Lymphoma
• Interventions: Biological: Autologous hematopoietic stem cell transplantation combined with CD19 CAR-T cells

• Registration Number: NCT05239676
• Lead Sponsor: Zhejiang University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-12-01
• Status Verified: 2022-02
• Study First Submitted QC: 2022-02-13
• Last Update Submitted: 2022-02-13
• Study First Posted: 2022-02-15
• Last Update Posted: 2022-02-15
• Study Start: 2022-02-28
• Primary Completion: 2024-12-01
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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)

  1. The subject did not remission or relapsed after receiving second-line or higher-line chemotherapy
  2. Primary resistance
  3. 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:

  1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
  2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
  3. Pregnant (or lactating) women;
  4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
  5. Active infection of hepatitis B virus or hepatitis C virus;
  6. Those who have used any gene therapy products before.
  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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment of Lymphoma	Autologous hematopoietic stem cell transplantation combined with CD19 CAR-T cells	Refractory and relapsed malignant lymphoma

Primary Outcome Measures

Name	Time	Method
overall response rate	Up to 30 months	the number of response patients/the number of total patients
Incidence of treatment-emergent adverse events (TEAEs)	24 months after cell infusion	Incidence of treatment-emergent adverse events \[Safety and Tolerability\]

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	Month 6,12,18and 24	Assessment of PFS at Month 6,12,18and 24
Overall survival (OS)	Month 6,12,18and 24	Assessment of OS at Month 6,12,18and 24
Duration of response(DOR)	Month 6,12,18and 24	Assessment of OS at Month 6,12,18and 24
Overall response rate(ORR)	Month 1,3,6,12,18and 24	Assessment of ORR (ORR = CR + CRi ) at Month 1,3,6,12,18and 24

Trial Locations

Locations (1)

The first affiliated hospital of medical college of zhejiang university; 🇨🇳 Hangzhou, Zhejiang, China