CD19/CD20 Dual-CAR-T in B-cell Leukemia Patients

Phase 1

Completed

• Conditions: B-cell Leukemia
• Interventions: Biological: CD19/CD20 Dual-CAR-T cells

• Registration Number: NCT04260945
• Lead Sponsor: Hebei Yanda Ludaopei Hospital

Brief Summary

This is a single center, single arm, open-label, phase I study to evaluate the safety and efficacy of CD19/CD20 Dual-CAR-T cells in patients with refractory and relapsed B-cell leukemia.

Detailed Description

This Phase I study is designed as a pilot trial evaluating the safety and efficacy of CD19/CD20 Dual-CAR-T cell therapy in subjects with refractory and relapsed B cell leukemia. Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -5, -4 and -3 followed by infusion of CD19/CD20 Dual-CAR-T cells. Safety and efficacy of CD19/CD20 Dual-CAR-T cells therapy will be monitored. The purpose of current study is to determine the clinical efficacy and safety of CD19/CD20 Dual-CAR-T cells therapy in patients with refractory and relapsed B-cell leukemia.

Study Timeline

• Study First Submitted: 2020-02-06
• Study First Submitted QC: 2020-02-06
• Study First Posted: 2020-02-07
• Study Start: 2020-03-10
• Status Verified: 2021-08
• Primary Completion: 2021-10-10
• Study Completion: 2022-02-10
• Last Update Submitted: 2022-03-06
• Last Update Posted: 2022-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Relapsed and refractory 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. Double positive expression of CD19 / CD20 in B cells;

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

6. ECOG score 0-3 points;

7. 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.

8. Patients who voluntarily sign informed consent and are willing to comply with treatment plans.

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/CD20 Dual-CAR-T cells	CD19/CD20 Dual-CAR-T cells	CD19/CD20 Dual-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 participants with adverse events.	6 months
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
Overall-Survival(OS)	6 months
Relapse-Free Survival(RFS )	6 months
Persistence of CAR-T cells in vivo	6 months

Trial Locations

Locations (1)

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