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

Early Phase 1

Not yet recruiting

• Conditions: T-cell Non-Hodgkin's Lymphoma
• Interventions: Drug: CD147- CAR T cells

• Registration Number: NCT05013372
• Lead Sponsor: Peking University People's Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-08-16
• Study First Submitted QC: 2021-08-18
• Study First Posted: 2021-08-19
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-01
• Last Update Posted: 2022-08-02
• Study Start: 2023-01
• Primary Completion: 2024-01-01
• Study Completion: 2025-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose-escalation	CD147- CAR T cells	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

Primary Outcome Measures

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

Secondary Outcome Measures

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