Sequential Low-dose Decitabine With PD-1/CD28 CD19 CAR-T in Relapsed or Refractory B-cell Lymphoma

Sequential Low-dose Decitabine Therapy With Novel CAR-T Carrying PD-1/CD28 Chimeric Switch Receptor in Relapsed or Refractory B-cell Lymphoma

To evaluate the efficacy and safety of CD19 PD-1/CD28-CAR-T sequential low-dose decitabine in the treatment of relapse or refractory B cell lymphoma.

Study Overview

• Status: Recruiting
• Conditions: Objective Response Rate
• Intervention / Treatment: Biological: CD19 PD-1/CD28 CAR-T Plus Low Dose Decitabine

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hui Liu, MD, PhD; Phone Number: 13819198629; Email: sylenliu@zju.edu.cn
• Study Contact Backup: Name: Wenbin Qian, MD, PhD; Phone Number: 13605801032; Email: qianwb@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 3100019
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1) Age ≥ 18, upper limit 75, unlimited for men and women;

  (2) ECOG score 0-3;

  (3) Histologically confirmed diffuse large B-cell lymphoma (DLBCL) [according to who 2008];

  (4) CD19 was positive (immunohistochemistry or flow cytometry).

  (5) The definition of refractory or relapse of DLBCL is: no complete remission after 2-line treatment; disease progression in any treatment process, or disease stabilization time equal to or less than 6 months; or disease progression or relapse within 12 months after hematopoietic stem cell transplantation;

  (6) The previous treatment of diffuse large B cell lymphoma must include rituximab (CD20 mAb) and anthracycline;

  (7) There should be at least one measurable focus. It is required that any length of lymph node focus should be greater than 1.5cm or any length of extranodal focus should be greater than 1.0cm. PET-CT scan focuses should have uptake (SUV is greater than liver blood pool);

  (8) The absolute value of neutrophils in peripheral blood ≥ 1000 / μ L, platelet ≥ 45000 / μ L;

  (9) Heart, liver and kidney function: creatinine < 1.5mg/dl; ALT (alanine aminotransferase) / AST (aspartate aminotransferase) 2.5 times lower than the normal upper limit; total bilirubin < 1.5mg/dl; heart ejection fraction (EF) ≥ 50%;

  (10) Sufficient understanding ability and voluntary signing of informed consent;

  (11) Those with fertility must be willing to use contraceptive methods;

  (12) According to the judgment of the researchers, the expected survival time is more than 4 months;

  (13) Willing to follow visit schedule, administration plan, laboratory inspection and other test steps.

Exclusion Criteria:

• (1) History of other tumors;

  (2) Hematopoietic stem cell transplantation was performed within 6 weeks;

  (3) Any target car-t treatment was performed within 3 months before the car-t treatment;

  (4) Previous use of any commercially available PD-1 mAb;

  (5) Cytotoxic drugs, glucocorticoids and other targeted drugs were received within 2 weeks before cell collection;

  (6) Active autoimmune diseases;

  (7) Uncontrollable infection of active bacteria and fungi;

  (8) HIV infection, syphilis infection; active hepatitis B or C: hepatitis B: HBV-DNA ≥ 1000IU / ml; hepatitis C: HCV RNA positive and liver function abnormal.

  (9) Known central nervous system lymphoma.

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: CD19 PD-1/CD28 CAR-T Plus Low Dose Decitabine	Biological: CD19 PD-1/CD28 CAR-T Plus Low Dose Decitabine; CD19 PD-1/CD28 CAR-T Plus Low Dose Decitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Objective response rate of the combination	3 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2021
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: April 18, 2021
• First Submitted That Met QC Criteria: April 18, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: June 5, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: IR2021001123

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