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

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

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.

Study Overview

• Status: Unknown
• Conditions: Lymphoma; Leukemia
• Intervention / Treatment: Biological: Anti-CD19-CAR γδT

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.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Beijing DOING Biomedical Co., Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: 1; Acute lymphoblastic leukemia treated with chimeric antigen receptor modified γδT cells(Anti-CD19-CAR γδT) targeting CD19.	Biological: Anti-CD19-CAR γδT; Cells extracted, followed by induction chemotherapy before Anti-CD19-CAR γδT infusion (dose escalation.)
Experimental: Experimental: 2; Chronic lymphoblastic leukemia with chimeric antigen receptor modified γδT cells(Anti-CD19-CAR γδT) targeting CD19.	Biological: Anti-CD19-CAR γδT; Cells extracted, followed by induction chemotherapy before Anti-CD19-CAR γδT infusion (dose escalation.)
Experimental: Experimental: 3; Non-hodgkin lymphoma treated with chimeric antigen receptor modified γδT cells(Anti-CD19-CAR γδT) targeting CD19.	Biological: Anti-CD19-CAR γδT; Cells extracted, followed by induction chemotherapy before Anti-CD19-CAR γδT infusion (dose escalation.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events of each patient.	Adverse events of each patient will be recorded and analysed.	3 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Beijing Doing Biomedical Co., Ltd.
• Investigators: Study Chair: Li gangyi, master, Beijing Doing Biomedical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2017
• Primary Completion (Anticipated): April 1, 2019
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: January 12, 2016
• First Submitted That Met QC Criteria: January 12, 2016
• First Posted (Estimate): January 14, 2016

Study Record Updates

• Last Update Posted (Actual): September 5, 2017
• Last Update Submitted That Met QC Criteria: September 1, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Lymphoma; Leukemia; CAR γδT
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: Doing-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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