Clinical trial NCT05239676: Autologous Hematopoietic Stem Cell Transplantation Combined With CAR-T Cells in the Treatment of Refractory and Relapsed Malignant Lymphoma
Official title: 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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Lymphoma
Keywords: ASCT
CD19 CAR-T
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2022-02-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: overall response rate
timeFrame: Up to 30 months
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: 24 months after cell infusion
Secondary outcomes:
measure: Overall response rate(ORR)
timeFrame: Month 1,3,6,12,18and 24
measure: Progression-free survival (PFS)
timeFrame: Month 6,12,18and 24
measure: Overall survival (OS)
timeFrame: Month 6,12,18and 24
measure: Duration of response(DOR)
timeFrame: Month 6,12,18and 24
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Zhejiang University
name: He Huang, PhD
role: PRINCIPAL_INVESTIGATOR
References: