CD147-CAR T Cells for Relapsed/Refractory T Cell Non-Hodgkin's Lymphoma

A Pioneering Study on the Safety and Efficacy of CD147-Chimeric Antigen Receptor (CAR) T Cells in Patients With Relapsed or Refractory T-cell Non-Hodgkin's Lymphoma

The safety and preliminary effectiveness of CD147-CAR T cells in patients with relapsed or refractory T cell non-Hodgkin's lymphoma will be investigated in this pioneering study.

Study Overview

• Status: Not yet recruiting
• Conditions: T-cell Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: CD147- CAR T cells

Detailed Description

CD147 has been demonstrated higher and relatively specific expression on T cell non-Hodgkin's lymphoma. Preclinical studies have shown that CAR T cells targeting CD147 antigen can continuously eliminate Jurkat T-cell lymphoma in mice and extend survival without severe adverse events including hemolysis. Preliminary investigation of CD147-CAR T cells in solid tumors has started and shown an acceptable safety profile. The safety and preliminary effectiveness of CD147-CAR T cells in patients with relapsed or refractory T cell non-Hodgkin's lymphoma will be investigated in this pioneering study.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Shenmiao Yang, MD.; Phone Number: 13439999810; Email: yangshenmiao@hotmail.com
• Study Contact Backup: Name: Xiaojun Huang, MD. PhD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The subject must meet all of the following criteria:

  1. 18-65 years old;
  2. Relapsed or refractory T-NHLs, including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK-positive ALCL, ALK-negative Image result for anaplastic large cell lymphoma (ALCL), enteropathy-related T-cell lymphoma, hepatosplenic T-cell lymphoma, etc.;
  3. Previously received ≥2 lines of treatment without a complete response;
  4. Immunohistochemical detection of tumor cells CD147 positive;
  5. ECOG score 0-2;
  6. The collection of mononuclear cells can be performed upon the judgment of the researcher;
  7. No contraindications for allogeneic hematopoietic stem cell transplantation (AlloHCT);
  8. Have donors for AlloHCT;
  9. Agree for sequential treatment of AlloHCT;

  10. Without serious organ dysfunction in 2 weeks before CAR-T infusion:

      1. Heart: without arrhythmia, LVEF≥50%, and without pericardial effusion; without heart failure (NYHA class III or IV) within12 months before CAR-T infusion; without myocardial infarction within 12 months before CAR-T infusion; without long-QT syndrome or secondary QT interval prolongation;
      2. Liver: ALT<2 times the upper limit of normal (ULN) and TBIL<1.5 times ULN, without active hepatitis;
      3. APTT and PT<1.5 times ULN;
      4. Kidney: Serum creatinine <1.5 mg/dl; or if the serum creatinine exceeds the upper limit, eGFR (CKD-EPI formula) needs to be > 50 ml/min;
      5. Fingertip blood oxygen saturation ≥ 92%.
  11. Estimated survival ≥ 3 months;
  12. Sexually active patients must be willing to use an effective method of birth control during the study period and within 6 months after the study ending, and male partners should use condoms;
  13. The patient is willing to join this clinical trial and sign an informed consent.

Exclusion Criteria:

• Anyone who has one or more of the following:

  1. A history of other malignancies with a disease-free period < 5 years (except for cured basal cell carcinoma of the skin, cured cervical carcinoma in situ, and gastrointestinal tumors proven to be cured by endoscopic mucosal resection);
  2. Those who have received allogeneic hematopoietic stem cell transplantation or organ transplantation;
  3. Patients with bone marrow involvement;
  4. Those who are allergic to the biological agents in CAR-T cell product ;
  5. Pregnant or breastfeeding;
  6. Active bacterial, fungal or viral infection;
  7. Receiving systemic hormone therapy 1 week before participating in the clinical trial;
  8. Have received other gene therapy before;
  9. HBV or HCV infection or carrier is defined as: HBsAg positive or HBV-DNA positive; anti-HCV positive and HCV-RNA positive;
  10. Active HIV infection;
  11. Clinical diagnosis of virus infection or uncontrolled virus activation, including cytomegalovirus (CMV), adenovirus (ADV), BK virus or human herpesvirus 6 (HHV-6), etc.;
  12. Central nervous system lymphoma (CNSL) is defined as the presence of ≥5 tumor cells/ ul in cerebrospinal fluid (CSF) or MRI suggested CNSL; any other CNS diseases, such as uncontrolled epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease or any autoimmune disease involving the central nervous system, or received treatment for central nervous system or brain metastasis (radiotherapy, surgery or other treatments);
  13. Imaging determined lung infection;
  14. Inappropriate to participate in the trial with investigators' decision.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Dose-escalation; Dose -1：0.1×10E+6/kg Dose 1：0.25×10E+6/kg Dose 2：0.5×10E+6/kg Dose 3：1.0×10E+6/kg Dose 4：2.0×10E+6/kg	Drug: CD147- CAR T cells; CAR T cells targeting CD147; Other Names: CAR T cells targeting CD147

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	The highest dose that does not cause unacceptable side effects.	within 12 months
Dose-limiting toxicity (DLT)	Side effects serious enough to prevent an increase in dose.	within 12 months
Adverse events	Adverse events	within 12 months
Serious adverse events (SAE)	Serious adverse events (SAE)	within 12 months
Adverse events of special interest (AESI)		within 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Overall response rate (ORR) evaluated according to the Lugano2014 criteria	At the 12th week, 6th month, 9th month and 12th month
Complete response rate (CR)	Complete response rate (CR) evaluated according to the Lugano2014 criteria	At the 12th week, 6th month, 9th month and 12th month
Duration of response (DOR)	Duration of response (DOR)	At the 12th week, 6th month, 9th month and 12th month
Cmax of CD147-CAR T cells		within 4 weeks
Tmax of CD147-CAR T cells		within 4 weeks
AUC of CD147-CAR T cells		within 4 weeks

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Xiaojun Huang, MD. PhD., Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2023
• Primary Completion (ANTICIPATED): January 1, 2024
• Study Completion (ANTICIPATED): January 1, 2025

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (ACTUAL): August 19, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 2, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: CD147; CAR T cells; T-cell Non-Hodgkin's lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell
• Other Study ID Numbers: CD147-CAR T for R/R T-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