Clinical trial NCT05013372: CD147-CAR T Cells for Relapsed/Refractory T Cell Non-Hodgkin's Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: T-cell Non-Hodgkin's Lymphoma
Keywords: CAR T cells
T-cell Non-Hodgkin's lymphoma
CD147
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2021-08-19
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: within 12 months
measure: Dose-limiting toxicity (DLT)
timeFrame: within 12 months
measure: Adverse events
timeFrame: within 12 months
measure: Serious adverse events (SAE)
timeFrame: within 12 months
measure: Adverse events of special interest (AESI)
timeFrame: within 12 months
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: At the 12th week, 6th month, 9th month and 12th month
measure: Complete response rate (CR)
timeFrame: At the 12th week, 6th month, 9th month and 12th month
measure: Duration of response (DOR)
timeFrame: At the 12th week, 6th month, 9th month and 12th month
measure: Cmax of CD147-CAR T cells
timeFrame: within 4 weeks
measure: Tmax of CD147-CAR T cells
timeFrame: within 4 weeks
measure: AUC of CD147-CAR T cells
timeFrame: within 4 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Peking University People's Hospital
name: Xiaojun Huang, MD. PhD.
role: PRINCIPAL_INVESTIGATOR
References: