Safety and Efficacy of Sequential CD19 and CD22 Targeted CAR-T Therapy for Relapsed/Refractory B Cell Lymphoma

Phase 1/Phase 2 Study of Sequential Chimeric Antigen Receptor T Cell Targeting at CD19 and CD22 B-cell Antigens Treating Refractory or Relapsed B-cell Lymphoma Patients

This is a single arm study to evaluate the efficacy and safety of Sequential CD19 and CD22 targeted CAR-T cells therapy for patients with relapsed/refractory B Cell Lymphoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma, B-Cell
• Intervention / Treatment: Biological: CD19 and CD22 targeted CAR-T cells

Detailed Description

Although the CD19 targeted CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell Leukemia and Lymphoma. There are some patients who resisted anti-CD19 CAR-T cells or get CD19 negative relapse. To make further improvement, We launch such a clinical trial using sequential CD19 and CD22 targeted CAR-T cells for patients with relapsed and refractory B Cell Lymphoma to evaluate the efficacy and safety of sequential CD19 and CD22 targeted CAR-T cell therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Hebei
    • Langfang, Hebei, China, 065201
      • Hebei Yanda Ludaopei Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 66 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Relapsed or refractory B cell non-hodgkin lymphoma.
2. KPS>60.
3. Life expectancy>12 weeks.
4. Gender unlimited, age from 3 years to 70 years.
5. Evidence for cell membrane CD19 and/or CD22 expression;
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. Pregnancy and nursing females.
2. Patients are allergic to cytokines.
3. Uncontrolled active infection.
4. Acute or chronic GVHD.
5. Treated with T cell inhibitor.
6. Patients who had used steroid hormones within one week.
7. Patients who had used Rituximab within two weeks.
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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: arm 1; sequential CD19 and CD22 targeted CAR-T cells treat

Biological: CD19 and CD22 targeted CAR-T cells; CAR-T cells were manufactured from peripheral blood mononuclear cells collected by leukapheresis and frozen for multiple uses. Before each CAR T-cell infusion (day 0), patients received lymphodepleting chemotherapy composing of Fludarabine (30 mg/m2/day) and Cyclophosphamide (300 mg/m2/day) on days -5 to -3. No bridging chemotherapy was given between enrollment and infusion. In sequential CAR-T clinical trials, CAR-T cells will be given.（anti-CD19 CAR-T first, then anti-CD22 CAR-T).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events that related to treatment	Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).	1 years
Overall remission rate (ORR)	The ORR of Sequential CD19 and CD22 CAR-T treatment will be recorded and assessed according to the revised 2014 Lugano Criteria.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete response(CR)	The CR of Sequential CD19 and CD22 CAR-T treatment will be recorded and assessed according to the revised 2014 Lugano Criteria.	24 months
partial response(PR)	The PR of Sequential CD19 and CD22 CAR-T treatment will be recorded and assessed according to the revised 2014 Lugano Criteria.	24 months
stable disease(SD)	The SD of Sequential CD19 and CD22 CAR-T treatment will be recorded and assessed according to the revised 2014 Lugano Criteria.	24 months
progressive disease(PD)	The PD of Sequential CD19 and CD22 CAR-T treatment will be recorded and assessed according to the revised 2014 Lugano Criteria.	24 months
Duration of remission (DOR)	DOR will be assessed from the first assessment of CR/CRi to the first assessment of recurrence or progression of the disease or death from any cause.	24 months

Collaborators and Investigators

• Sponsor: Kecellitics Biotech Company Ltd
• Collaborators: Hebei Yanda Ludaopei Hospital
• Investigators: Study Chair: li xiangqun, doctor, Kecellitics Biotech Company Ltd

Study record dates

Study Major Dates

• Study Start (Anticipated): December 10, 2022
• Primary Completion (Anticipated): December 10, 2024
• Study Completion (Anticipated): December 10, 2025

Study Registration Dates

• First Submitted: November 26, 2022
• First Submitted That Met QC Criteria: December 6, 2022
• First Posted (Estimate): December 14, 2022

Study Record Updates

• Last Update Posted (Estimate): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: CAR-T; Lymphoma
• 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
• Other Study ID Numbers: Kece-4

Drug and device information, study documents

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