Efficacy and Safety of PZ01 Treatment in Patients With r/r CD19+ B-cell Acute Lymphoblastic Leukemia/B Cell Lymphoma

Study of Anti-CD19 Chimeric Antigen Receptor T Cells（PZ01） for Relapsed/ Refractory B-cell Acute Lymphoblastic Leukemia/B Cell Lymphoma

The major aim of this research is to assess the feasibility, safety and effectiveness of CD19 CAR-T Cell Therapy for Relapsed/ Refractory Acute Lymphoblastic Leukemia/ B cell Lymphoma patients who have applied it.

Study Overview

• Status: Unknown
• Conditions: B-cell Lymphoma; B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: PZ01 CAR-T cells

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100048
      • Recruiting
      • Department of Hematology, Navy General Hospital of PLA
      • Contact: Lixin Wang; Phone Number: 86-013718000488; Email: wgy@pinzelife.com
      • Principal Investigator: Jianliang Shen
      • Sub-Investigator: Lixin Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects or their legal guardians participate in this experiment voluntarily and informed consent form must be signed
2. In accordance with National Comprehensive Cancer Network (NCCN) ALL Guidelines for Patients (2016, v.1) and CD19+B-ALL/B cell lymphoma patients diagnosed by histology

3. In accordance with r/r CD19+ B-ALL/B cell lymphoma diagnosis, including any of the following situations:

   1. Getting through 2 treatments of standard chemotherapy with CR not yet obtained
   2. Reach CR for the first inducement, but CR lasts for ≦12 months
   3. r/r CD19+ B-ALL/B cell lymphoma for no positive effect after first or repeated remedial treatment
   4. ≧2 times of recurrence
4. Remedial chemotherapy is not used within 4 weeks before cell therapy
5. Immunosuppressive drug is not used within 4 weeks before cell therapy, including but not limited to systemic hormone therapy
6. Antibody drug treatment is not received within 2 weeks before cell therapy
7. Normal cardiac motion shown by echocardiography, left ventricular ejection fraction (LVEF) ≥50%, with no pericardial effusion and severe symptoms of cardiac arrhythmia
8. No pulmonary active infection is found, with normal pulmonary function and indoor air SaO2 ≧92%
9. No contraindications for leukapheresis
10. Expected survival >3 months
11. Grade 0 or 1 of ECOG performance status

Exclusion Criteria:

1. Pregnant and breastfeeding women
2. Uncontrolled active infection
3. Uncontrolled infectious disease is diagnosed, such as HIV, syphilis, hepatitis A, hepatitis B, hepatitis C and E.
4. Patients who have used a large amount of glucocorticoid or other immunosuppressive drugs within 4 weeks
5. Stage II-IV Acute/chronic general graft versus host disease
6. Gene therapy has been undergone in the past

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PZ01 CAR-T Cells; This is a phase I study. Patients with relapsed/ refractory B-cell Acute Lymphoblastic Leukemia/B cell Lymphoma are eligible for enrollment.

Drug: PZ01 CAR-T cells; Chimeric antigen receptor (CAR) T cells targeting CD19 will be evaluated for safety and efficacy in patients with relapsed/ refractory B-cell Acute Lymphoblastic Leukemia/B cell Lymphoma. The CAR consists of a CD19 targeting antibody scFv with two intracellular signaling domains derived from CD3 zeta and 4-1BB. Autologous T cells will be gene-engineered with the CAR gene using a lentivirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Related Adverse Events	To evaluate the safety of adoptive transfer of gene-modified autologous CD19-specific T cells in relapsed/ refractory B-cell Acute Lymphoblastic Leukemia/B cell Lymphoma.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Proportion of patients with reduction in tumor burden.	2 months
Overall survival (OS)	Time from study enrollment until death.	6 months
Minimal residual disease negative remission rate(MRD)	Proportion of MRD-negative patients.	2 months

Collaborators and Investigators

• Sponsor: Pinze Lifetechnology Co. Ltd.
• Collaborators: Chinese Academy of Sciences; Navy General Hospital, Beijing
• Investigators: Principal Investigator: Shengdian Wang, Insitute of Biophysics,Chinese Academy of Sciences

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2017
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: September 9, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (Actual): September 13, 2017

Study Record Updates

• Last Update Posted (Actual): September 15, 2017
• Last Update Submitted That Met QC Criteria: September 14, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: PZ01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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