Phase I Study of pCAR-19B in the Treatment of Adult CD19-positive Relapsed/Refractory B-ALL

A Phase I Clinical Study of Anti-CD19 CAR-T Therapy (pCAR-19B) in the Treatment of Adult CD19-positive Relapsed/Refractory B-ALL

This is a phase I clinical study to evaluate the safety and tolerability of pCAR-19B in adults with relapsed or refractory B-ALL, and to obtain the maximum tolerated dose of pCAR-19B and phase II Recommended dose.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia, in Relapse; Refractory Acute Lymphoblastic Leukemia
• Intervention / Treatment: Biological: pCAR-19B cells

Detailed Description

This is a single-center, single-arm, open-label study. The study plans to set up 3 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 9-18 adults with relapsed or refractory B-ALL.pCAR-19B will be infused to the subject by intravenous infusion.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiaoxi zhou, M.D; Phone Number: 86-27-83665027; Email: cello316@163.com
• Study Contact Backup: Name: Liang Huang, M.D; Phone Number: 86-27-63639810; Email: lhuang@tjh.tjmu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
      • Contact: Liang Huang, M.D; Phone Number: 86-27-63639810; Email: lhuang@tjh.tjmu.edu.cn
      • Contact: Xiaoxi Zhou, M.D; Phone Number: 86-27-83665027
      • Principal Investigator: Jianfeng zhou, M.D. Ph.D
      • Sub-Investigator: Xiaoxi Zhou, M.D
      • Sub-Investigator: Liang Huang, M.D
      • Sub-Investigator: Jia Wei, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosed with B-ALL，and meet one of the following conditions:

   1. First-line or multiple-line salvage chemotherapy did not achieve complete remission；
   2. Early relapse after complete remission (<12 months), or late relapse after complete remission (≥12 months) and complete remission has not been achieved after 1 course of treatment；
   3. Relapse after autologous or allogeneic hematopoietic stem cell transplantation;
2. Ph+ALL patients should also receive at least two TKI treatments；

3. For allogeneic hematopoietic stem cell transplant subjects, the following conditions must be met：

   1. Allo-HSCT takes ≥6 months before pCAR-19B infusion；
   2. No GVHD of grade 2 or above occurred within 2 weeks before PBMC collection;
4. Express CD19;
5. 22~70 years old, no gender limit;
6. The expected survival time is more than 12 weeks;
7. KPS>60;
8. No serious mental disorders;

9. The function of important organs is basically normal:

   1. Heart function: echocardiography indicates that the cardiac ejection fraction is ≥50%, and the electrocardiogram has no obvious abnormalities;
   2. Renal function: serum creatinine≤2.0×ULN;
   3. Liver function: ALT and AST ≤3.0×ULN;
   4. Total bilirubin and alkaline phosphatase≤2.0×ULN (Gilbert syndrome ≤ 3.0×ULN);
   5. Blood oxygen saturation>92%.
10. Have standards for apheresis or venous blood collection, and no other cell collection contraindications;
11. The patient himself or his guardian agrees to participate in the clinical trial and signs the ICF, indicating that he understands the purpose and procedures of the clinical trial and is willing to participate in the research.

Exclusion Criteria:

1. With central nervous system disease at the time of screening;
2. Have received CAR-T therapy or other genetically modified cell therapy;
3. Participated in other clinical studies within 1 month before screening;
4. Have received the following anti-tumor treatments before screening: received chemotherapy, targeted therapy or other experimental drug treatments within 14 days or at least 5 half-lives (whichever is shorter);
5. Have received a live attenuated vaccine within 4 weeks before screening;
6. Cerebrovascular accident or seizure occurred within 6 months before signing the ICF;

7. Suffered from any of the following heart diseases:

   1. NYHA stage III or IV congestive heart failure;
   2. Myocardial infarction or CABG occurred ≤6 months before enrollment;
   3. Clinically significant ventricular arrhythmia, or history of unexplained syncope (except for cases caused by vasovagal or dehydration);
   4. History of severe non-ischemic cardiomyopathy.
8. Uncontrollable infection in the 2 weeks before screening；
9. Active autoimmune diseases；
10. Patients with malignant tumors other than acute lymphoblastic leukemia within 5 years before screening, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical resection, and duct in situ after radical resection cancer；
11. HBsAg or HBcAb positive and HBV DNA is greater than the normal range; HCV antibody is positive and HCV RNA greater than the normal range; HIV antibody positive; syphilis positive; CMV DNA positive;
12. Women who are pregnant or breastfeeding, and male or female subjects who plan to have children within 1 year after receiving pCAR-19B cell reinfusion;
13. Other situations considered by the researcher to be unsuitable to participate in the study.

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: pCAR-19B cells; Infusion of pCAR-19B cells by dose-escalating	Biological: pCAR-19B cells; Drug: pCAR-19B cells； Administration method: intravenous infusion； Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse events after pCAR-19B infusion [Safety and Tolerability]	Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)	28 days
Obtain the maximum tolerated dose of pCAR-19B cells[Safety and Tolerability]	Dose-limiting toxicity after cell infusion	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CMAX of pCAR-19B cells [Cell dynamics]	CMAX is defined as the highest concentration of pCAR-19B cells expanded in peripheral blood	3 months
TMAX of pCAR-19B cells [Cell dynamics]	TMAX is defined as the time to reach the highest concentration	3 months
Objective response rate after pCAR-19B infusion [Effectiveness]	Objective response rate includes CR, CRi	3 months
AUCS of pCAR-19B cells [Cell dynamics]	AUCS is defined as the area under the curve in 28 days and 90 days	3 months
Pharmacodynamics of pCAR-19B cells[Cell dynamics]	Cytokines such as hs-CRP, IL-6 levels	3 months
Immunogenicity of pCAR-19B cells	Anti-CAR antibody	3 months

Collaborators and Investigators

• Sponsor: Chongqing Precision Biotech Co., Ltd
• Investigators: Principal Investigator: Jianfeng Zhou, M.D. Ph.D, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2020
• Primary Completion (Anticipated): January 30, 2022
• Study Completion (Anticipated): March 28, 2022

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 17, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2021
• Last Update Submitted That Met QC Criteria: May 12, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: CD19; Adoptive T Cell Therapy; Chimeric antigen receptor
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: PB02

Drug and device information, study documents

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