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

Phase I Study of T 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 autologous T-cells in patients with high risk, relapsed CD19+ haematological malignancies.

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma; Leukemia
• Intervention / Treatment: Biological: Anti-CD19-CAR

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) T-cells (CD19 CAR T-cells) in patients with high risk, relapsed CD19+ haematological malignancies (Leukemia and lymphoma). Following informed consent and registration to the trial, patients will undergo an unstimulated leukapheresis for the generation of the CD19 CAR T-cells. Patients will receive the CD19CAR T-cells following lymphodepleting chemotherapy. The study will evaluate the safety, efficacy and duration of response of the CD19 CAR T-cells in patients with high risk relapsed CD19+ malignancies.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: gai liyun, doctor; Phone Number: 086-13269099630; Email: liyun_gai@doingtimes.com

Study Locations

• China
  • Beijing, China, 100021
    • Beijing DOING Biomedical Co., Ltd
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University
  • Hebei
    • Sanhe, Hebei, China, 065200
      • Hebei Yanda Ludaopei Hospital
      • Contact: Gai liyun, Doctor; Phone Number: 086-13269099630
  • Henan
    • Luoyang, Henan, China, 471003
      • First Affiliated Hospital of Henan University of Science and Technology
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University
  • Jiangsu
    • Huaian, Jiangsu, China, 223300
      • Huai'an first people's hospital
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • First Hospital of Jilin University
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Shanxi Dayi Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300121
      • Tianjin People's Hospital
      • Contact: Li gangyi, Master; Phone Number: 13601204100; Email: gangyi_li@doingtimes.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310002
      • Hangzhou Cancer Hospital

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 trial.

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: Non-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 T cells(Anti-CD19-CAR) targeting CD19.	Biological: Anti-CD19-CAR; Cells extracted, followed by induction chemotherapy before CD19-CAR infusion (dose escalation.)
Experimental: Experimental: 2; Chronic lymphoblastic leukemia with chimeric antigen receptor modified T cells(Anti-CD19-CAR) targeting CD19.	Biological: Anti-CD19-CAR; Cells extracted, followed by induction chemotherapy before CD19-CAR infusion (dose escalation.)
Experimental: Experimental: 3; Non-hodgkin lymphoma treated with chimeric antigen receptor modified T cells(Anti-CD19-CAR) targeting CD19.	Biological: Anti-CD19-CAR; Cells extracted, followed by induction chemotherapy before CD19-CAR infusion (dose escalation.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events of each patient.	Determine the toxicity profile of the CD19 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival time of Anti-CD19 CAR T cells in vivo.	To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood.	3 years
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
Maximum tolerated dose (MTD) of CD19 targeted CAR T cells.	Maximum tolerated dose (MTD) of CD19 targeted CAR T cells.	4 weeks

Collaborators and Investigators

• Sponsor: Beijing Doing Biomedical Co., Ltd.
• Collaborators: The First Hospital of Jilin University; Hebei Yanda Ludaopei Hospital
• Investigators: Study Chair: Li gangyi, master, Beijing Doing Biomedical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2021
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: September 8, 2015
• First Submitted That Met QC Criteria: September 9, 2015
• First Posted (Estimate): September 11, 2015

Study Record Updates

• Last Update Posted (Actual): January 26, 2021
• Last Update Submitted That Met QC Criteria: January 23, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Lymphoma; Leukemia; CAR T
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: Doing-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
• product manufactured in and exported from the U.S.: No