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

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

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

Study Overview

• Status: Recruiting
• Conditions: Lymphoma
• Intervention / Treatment: Biological: Autologous hematopoietic stem cell transplantation combined with CD19 CAR-T cells

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: He Huang, PhD; Phone Number: +8613605714822; Email: hehuangyu@126.com
• Study Contact Backup: Name: Yongxian Hu, PhD; Phone Number: +8615957162012; Email: huyongxian2000@aliyun.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university
      • Contact: Yongxian Hu, PhD; Phone Number: +8615957162012; Email: huyongxian2000@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment of Lymphoma; Refractory and relapsed malignant lymphoma	Biological: Autologous hematopoietic stem cell transplantation combined with CD19 CAR-T cells; 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

What is the study measuring?

Primary Outcome Measures

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

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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 28, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: February 13, 2022
• First Posted (Actual): February 15, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 13, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: ASCT; CD19 CAR-T
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: AUTO-CART-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No