CD19-CAR-T in B-cell Malignancies Patients

Phase 1

Completed

• Conditions: B-cell Malignancy
• Interventions: Biological: CD19-CAR-T cells

• Registration Number: NCT03952923
• Lead Sponsor: Hebei Yanda Ludaopei Hospital

Brief Summary

This is a single center, single arm, open-lable phase I study to determine the safety and efficacy of CD19-CAR-T cells in patients with refractory and relapsed B-cell malignancies.

Detailed Description

This Phase I study is designed as a pilot trial evaluating the safety and of CD19-CAR-T cell therapy in subjects with refractory and relapsed B cell malignancies. Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -5, -4 and -3 followed by infusion of CD19-CAR-T cells. Safety and efficacy of CD19-CAR-T cells therapy will be monitored. The purpose of current study is to determine the clinical efficacy and safety of CD19-CAR-T cells therapy in patients with refractory and relapsed B-cell malignancies.

Study Timeline

• Study First Submitted: 2019-02-25
• Study First Submitted QC: 2019-05-15
• Study First Posted: 2019-05-16
• Study Start: 2019-08-01
• Status Verified: 2020-08
• Primary Completion: 2021-01-01
• Study Completion: 2021-03-31
• Last Update Submitted: 2022-01-28
• Last Update Posted: 2022-02-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

1. Relapsed and refractory CD19 positive B-cell acute malignancies with:

   • Relapsed after competed remission, could not get competed remission after at more than 1 course of chemotherapy (including MRD≥0.1%);
   • MRD≥0.1% after allogeneic hematopoietic stem cell transplantation(HSCT), or recurrence after complete remission or MRD ≥ 0.1% after HSCT;
   • Refractory: at least two courses of chemotherapy did not achieve complete remission or MRD ≥ 0.1%;

2. Patients must have evaluable evidence of disease, including minimal residual disease (MRD);

3. Ph + patients who meet the following criteria can register:Failure to tolerate TKI or TKI treatment failure, or failure to transplant;

4. Ages 1 to 70 years, including boundary values;

5. ECOG score 0-3 points;

6. Women of childbearing age (15-49 years old) must receive a pregnancy test within 7 days prior to initiation of treatment and the results are negative; male and female patients with fertility must use an effective contraceptive to ensure 3 months after discontinuation of treatment during the study period not pregnant inside.

Exclusion Criteria

1. patients with organ failure:

   • Heart: NYHA heart function grade IV;
   • Liver: Grade C that achieves Child-Turcotte liver function grading;
   • Kidney: kidney failure and uremia;
   • Lung: symptoms of respiratory failure;
   • Brain: a person with a disability;

2. Active infections that are difficult to control;

3. Human immunodeficiency virus (HIV) positive;

4. Liver and kidney function: total bilirubin > 5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 5 × ULN, serum creatinine clearance rate 60mL / min;

5. GVHD ≥ 2 or anti-GVHD treatment;

6. Received allogeneic cell therapy within 4 weeks, such as donor lymphocyte infusion;

7. Subject received anti-tumor treatment (chemotherapy, mAb, or hormone) for less than 1 week;

8. Central nervous system white blood that is symptomatic or uncontrolled by systemic chemotherapy and intrathecal chemotherapy (a large number of tumor cells in CSF, white blood cell count >15WBCs/mL);

9. intracranial hypertension or unconsciousness; respiratory failure; diffuse vascular internal coagulation;

10. pregnant or lactating women;

11. The patient does not agree to use effective contraception during the treatment period and for the next 3 months;

12. Patients who participate in other clinical studies at the same time;

13. The investigator believes that there are other factors that are not suitable for inclusion or influence the subject's participation or completion of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD19-CAR-T cells	CD19-CAR-T cells	CD19-CAR-T cells are prepared via lentiviral infection. 5 days prior to infusion of CAR-T cells, subjects receive fludarabine at dose 30mg/m2/day and cyclophosphamide treatment at dose 250mg/m2 for 3 days and take a rest for 2 days before infusion.

Primary Outcome Measures

Name	Time	Method
Percentage of adverse events	6 months	Percentage of participants with adverse events.
Objective remission rate(ORR)	6 months	The percentage of participants who achieved complete remission (CR) and partial remission over all participants.

Secondary Outcome Measures

Name	Time	Method
Relapse-Free Survival(RFS )	6 months
Overall-Survival(OS)	6 months
Persistence of CAR-T cells in vivo	6 months

Trial Locations

Locations (1)

Hebei Yanda Ludaopei Hospital; 🇨🇳 Sanhe, Hebei, China