Immunotherapy With CD19 CAR γδT-cells for B-Cell Lymphoma, ALL and CLL

Overview

This study aims to evaluate the safety, efficacy and duration of response of CD19 Chimeric Antigen Receptor (CAR) redirected allogeneic γδT-cells in patients with high risk, relapsed CD19+ haematological malignancies.

Full Title of Study: “Phase I Study of γδT Cells Expressing an Anti-CD19 Chimeric Receptor in Children and Young Adults With B Cell Malignancies”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2019

Detailed Description

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product named CD19 Chimeric Antigen Receptor (CAR) γδT-cells (CD19 CAR γδT-cells) in patients with high risk, relapsed CD19+ haematological malignancies (Leukemia and lymphoma). Following informed consent and registration to the trial, Patients will receive the allogeneic CD19 CAR γδT-cells following lymphodepleting chemotherapy. The study will evaluate the safety, efficacy and duration of response of the CD19 CAR γδT-cells in patients with high risk relapsed CD19+ malignancies.

Interventions

  • Biological: Anti-CD19-CAR γδT
    • Cells extracted, followed by induction chemotherapy before Anti-CD19-CAR γδT infusion (dose escalation.)

Arms, Groups and Cohorts

  • Experimental: Experimental: 1
    • Acute lymphoblastic leukemia treated with chimeric antigen receptor modified γδT cells(Anti-CD19-CAR γδT) targeting CD19.
  • Experimental: Experimental: 2
    • Chronic lymphoblastic leukemia with chimeric antigen receptor modified γδT cells(Anti-CD19-CAR γδT) targeting CD19.
  • Experimental: Experimental: 3
    • Non-hodgkin lymphoma treated with chimeric antigen receptor modified γδT cells(Anti-CD19-CAR γδT) targeting CD19.

Clinical Trial Outcome Measures

Primary Measures

  • Adverse events of each patient.
    • Time Frame: 3 years
    • Adverse events of each patient will be recorded and analysed.

Secondary Measures

  • Survival time of Anti-CD19 CAR γδT cells in vivo.
    • Time Frame: 3 years
    • PCR will be applied to analyse the survival time of Anti-CD19 CAR γδT cells in vivo.
  • Antitumor Effects
    • Time Frame: Every 3 months post treatment up to 24 months
    • Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.
  • Maximum tolerated dose (MTD) of CD19 targeted CAR γδT cells.
    • Time Frame: 4 weeks
    • Maximum tolerated dose (MTD) of CD19 targeted CAR γδT cells.

Participating in This Clinical Trial

Inclusion Criteria

1. Relapsed or refractory B cell derived acute lymphoblastic leukemia(ALL), chronic lymphoblastic leukemia(CLL) and non-hodgkin lymphoma. 2. KPS>60. 3. Life expectancy>3 months. 4. Gender unlimited, age from 18 years to 70 years. 5. CD19 expression must be detected on greater than 15% of the malignant cells by immunohistochemistry or greater than 30% by flow cytometry. 6. Patients who have failed at least one line of a standard treatment. 7. No serious mental disorder. 8. Patients must have adequate cardiac function(no cardiac disease, LVEF≥40% ), adequate pulmonary function as indicated by room air oxygen saturation of >94%, and adequate renal function(Cr≤133umol/L). 9. No other serious diseases(autoimmune disease, immunodeficiency etc.). 10. No other tumors. 11. Patients volunteer to participate in the research. 12. Patients with history of allogeneic stem cell transplantation are eligible if at least 100 days post-transplant, if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to infusion. Exclusion Criteria:

1. KPS<50. 2. Patients are allergic to cytokines. 3. Central nervous system leukemia within 28 days. 4. Uncontrolled active infection. 5. Acute or chronic GVHD. 6. Treated with T cell inhibitor. 7. Pregnancy and nursing females. 8. HIV/HBV/HCV Infection. 9. Other situations we think improper for the research.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Beijing Doing Biomedical Co., Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Li gangyi, master, Study Chair, Beijing Doing Biomedical Co., Ltd.
  • Overall Contact(s)
    • Xie yanyun, master, +8615601041145, yanyun_xie@doingtimes.com

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