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

An Open, Uncontrolled, Multicenter Clinical Trial to Explore the Safety, Efficacy, and Remission Phase of Chimeric Antigen Receptor T Cell (CAR-T) in the Treatment of Relapsed Refractory (R/R) Non-Hodgkin Lymphoma (NHL)

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.

Study Overview

• Status: Recruiting
• Conditions: Refractory Indolent Adult Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: CD19 CAR-T; Drug: CD22 CAR-T; Drug: CD19+CD22 CAR-T; Drug: Fludarabine; Drug: Cyclophosphamide

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jianqiang Li, Phd&MD; Phone Number: 86-311-82970975; Email: hr@senlangbio.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • No.2 Hospital of Hebei Medical 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. 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;

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.

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: volunteers; 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

Drug: CD19 CAR-T; CD19 CAR-T for CD19 positive R/R non-Hodgkin lymphoma; Other Names: Senl_19; Drug: CD22 CAR-T; CD22 CAR-T for CD22 positive R/R non-Hodgkin lymphoma; Other Names: Senl_22; Drug: CD19+CD22 CAR-T; CD19+CD22 CAR-T for CD19 positive and CD22 positive R/R non-Hodgkin lymphoma; Other Names: Senl_19+22; Drug: Fludarabine; 25mg/㎡ for D-4、D-3 and D-2; Other Names: flu; Drug: Cyclophosphamide; 500mg/㎡ for D-3 and D-2; Other Names: ctx

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate of complete remission and partial remission	Objective response rate of complete remission and partial remission	24 months
Overall survival time	Overall survival time	24 months

Collaborators and Investigators

• Sponsor: Hebei Senlang Biotechnology Inc., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Anticipated): March 30, 2023
• Study Completion (Anticipated): March 30, 2023

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 11, 2020
• First Posted (Actual): November 13, 2020

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 11, 2020
• Last Verified: November 1, 2020

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; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: CAR-T for NHL

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
• product manufactured in and exported from the U.S.: No