CD19-CAR-T in B-cell Malignancies Patients

CD19-CAR-T for Patients With B Cell Malignancies

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.

Study Overview

• Status: Completed
• Conditions: B-cell Malignancy
• Intervention / Treatment: Biological: CD19-CAR-T cells

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hebei
    • Sanhe, Hebei, China, 065200
      • Hebei yanda Ludaopei Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Biological: 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Relapse-Free Survival(RFS )	6 months
Overall-Survival(OS)	6 months
Persistence of CAR-T cells in vivo	6 months

Collaborators and Investigators

• Sponsor: Hebei Yanda Ludaopei Hospital
• Collaborators: China Immunotech (Beijing) Biotechnology Co., Ltd.; Avalon GloboCare Corp.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2019
• Primary Completion (ACTUAL): January 1, 2021
• Study Completion (ACTUAL): March 31, 2021

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (ACTUAL): May 16, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 28, 2022
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: HXYT-002

Drug and device information, study documents

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