CAR-T Cells in Treating Patients With Relapsed or Refractory NHL

Early Phase 1

• Conditions: Refractory Indolent Adult Non-Hodgkin Lymphoma
• Interventions: Drug: CD19 CAR-T; Drug: CD22 CAR-T; Drug: CD19+CD22 CAR-T; Drug: Fludarabine; Drug: Cyclophosphamide

• Registration Number: NCT04626739
• Lead Sponsor: Hebei Senlang Biotechnology Inc., Ltd.

Brief Summary

This is an open, single-arm, phase I clinical study to evaluate efficacy and safety of chimeric antigen receptor T cell immunotherapy (CAR-T) in the treatment of Non-hodgkin's lymphoma. A total of 100 patients are planned to be enrolled over a period of 3 years.

Detailed Description

Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. In this study, investigators will evaluate their safety and efficacy in patients with different types of hematopoietic and lymphoid malignancies. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, tumor targeting and disease status after treatment will also be evaluated.

Study Timeline

• Study Start: 2020-04-01
• Status Verified: 2020-11
• Study First Submitted: 2020-11-06
• Study First Submitted QC: 2020-11-11
• Last Update Submitted: 2020-11-11
• Study First Posted: 2020-11-13
• Last Update Posted: 2020-11-13
• Primary Completion: 2023-03-30
• Study Completion: 2023-03-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Fully understand and voluntarily sign the informed consent, and are willing and able to comply with the visit, treatment protocol, laboratory examination and other requirements of the study as set out in the trial procedure sheet;

2. Cd19-positive R/R NHL patients: recurrent or refractory patients were defined as diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), mucosa-associated lymphoid tissue lymphoma (MALTL), and Burkit lymphoma (BL) diagnosed by histopathology.

   To standard treatment for primary drug resistance, or after treatment for at least two line standard specification treatment of PD, or the last treatment effect for SD and duration less than 6 months, or CD20 positive patients by the resistance against CD20 single treatment is invalid or has a relapse, or autologous hematopoietic stem cell transplantation in PD or 12 months after the confirmed by biopsy has a relapse, or to save patients after autologous hematopoietic stem cell transplantation for at the end of the line no ease or relapse after treatment;

3. There should be at least one measurable tumor focal point;

4. Karnofsky [2] score 50 or more;

5. Tumor cells were CD19 positive by immunohistochemistry or flow cytometry;

6. The expected survival time is greater than 3 months;

7. Pregnancy tests for women of childbearing age must be negative; Both men and women should agree to use effective contraceptives during treatment and for the following 1 year;

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Exclusion Criteria

1. Serious cardiac insufficiency, left ventricular ejection fraction<50;
2. Has a history of severe pulmonary function damaging;
3. Merging other malignant tumor;
4. Merging uncontrolled infection;
5. Merging the metabolic diseases (except diabetes);
6. Merging severe autoimmune diseases or immunodeficiency disease;
7. patients with active hepatitis B or hepatitis C;
8. patients with HIV infection;
9. Has a history of serious allergies on Biological products (including antibiotics);
10. Happened in 3 ~ 4 acute GvHD after allogeneic hematopoietic stem cell transplantation on recurring patients;
11. Pregnancy or lactation women;
12. Any situation that would increase dangerousness of subjects or disturb the outcome of the clinical study according to the researcher's evaluation.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
volunteers	CD19 CAR-T	The patient voluntarily signs the informed consent, and the patient meets the entry criteria to diagnose patients with Relapsed Refractory (R/R) non-Hodgkin lymphoma
volunteers	CD22 CAR-T	The patient voluntarily signs the informed consent, and the patient meets the entry criteria to diagnose patients with Relapsed Refractory (R/R) non-Hodgkin lymphoma
volunteers	CD19+CD22 CAR-T	The patient voluntarily signs the informed consent, and the patient meets the entry criteria to diagnose patients with Relapsed Refractory (R/R) non-Hodgkin lymphoma
volunteers	Fludarabine	The patient voluntarily signs the informed consent, and the patient meets the entry criteria to diagnose patients with Relapsed Refractory (R/R) non-Hodgkin lymphoma
volunteers	Cyclophosphamide	The patient voluntarily signs the informed consent, and the patient meets the entry criteria to diagnose patients with Relapsed Refractory (R/R) non-Hodgkin lymphoma

Primary Outcome Measures

Name	Time	Method
Number of Participants with Severe/Adverse Events as a Measure of Safety	28 days	Number of Participants with Severe/Adverse Events as a Measure of Safety
CAR-T Cell expansion level	24 months	Copies numbers of CAR in peripheral blood(PB) and/or bone marrow(BM)

Secondary Outcome Measures

Name	Time	Method
Objective response rate of complete remission and partial remission	24 months	Objective response rate of complete remission and partial remission
Overall survival time	24 months	Overall survival time

Trial Locations

Locations (1)

No.2 Hospital of Hebei Medical University; 🇨🇳 Shijiazhuang, Hebei, China