Clinical trial NCT04008394: Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies
Official title: Efficacy and Safety of Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies：a Single-center, Open, Single-arm Clinical Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Adult T-Cell Lymphoma/Leukaemia
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
NK/T-cell Lymphoma
Peripheral T Cell Lymphoma
Hodgkin Lymphoma
Keywords: CD-30 CART
Refractory/Relapsed
lymphocyte malignancies
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
Collaborators: name: Wuhan Bio-Raid Biotechnology Co, Ltd. China
First posted: 2019-07-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-center,Open,One-arm Clinical Study
Primary purpose: TREATMENT

Brief summary: The overall purpose of this study is to explore the safety and therapeutic effect of CD30-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of Refractory/Relapsed lymphocyte malignancies.

Detailed description: Chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) have the capabilities to recognize tumor associated antigen and kill tumor cells specifically. CD30 is originally described as a marker of Hodgkin's and R-S cells in Hodgkin's lymphoma. CD30 antibody has been applied to treat lymphocyte derived malignancies. To explore the potency of CD30 in CAR-T therapy, this trial is designed and conducted to test the safety and efficacy of CD30-targeted CAR-T in Refractory/Relapsed lymphocyte malignancies.

Eligibility criteria: Inclusion Criteria:

1. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
2. Male or female patients aged 18 to 70 years (including 18 and 70 years old).
3. Pathological and histological examination confirmed CD30+ lymphocyte malignancies, and patients currently have no effective treatment options, such as chemotherapy or recurrence after hematopoietic stem cell transplantation; or patients voluntarily choose Anti-CD30 CAR-T as rescue treatment.
4. CD30+ lymphocyte malignancies:

   1. Adult T-cell leukemia/lymphoma
   2. Anaplastic large cell lymphoma (ALCL);
   3. Angioimmunoblastic T-cell Lymphoma (AITL);
   4. NK/T-cell lymphoma;
   5. Peripheral T-cell lymphoma (PTCL);
   6. Hodgkin lymphoma;
5. Subjects:

   1. There are still residual lesions after major treatment, and they are not suitable for HSCT (auto/allo-HSCT);
   2. Recurrence occurs after CR1, and HSCT (auto/allo-HSCT) is not selected or suitable because of self-willingness;
   3. After hematopoietic stem cell transplantation or cellular immunotherapy, the patient suffered relapse or did not remission.
6. Having a measurable or evaluable lesion.
7. Patient's main organs function well：

   1. Liver function: ALT/AST \< 3 times the upper limit of normal (ULN) and
   2. total bilirubin≤34.2μmol/L
   3. Renal function: Creatinine \< 220μmol/L.
   4. Pulmonary function: Indoor oxygen saturation≥95%.
   5. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥40%.
8. The patients did not receive any anticancer treatments such as chemotherapy, radiotherapy and immunotherapy (such as immunosuppressive drugs) within 4 weeks before admission, and the toxicity related to previous treatments had returned to \< 1 level at admission (except for low toxicity such as alopecia).
9. The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
10. Patient ECOG score≤2, Estimated survival time≥3 months.

Exclusion Criteria:

1. Women who are pregnant (urine/blood pregnancy test positive) or lactating.
2. Male or female with a conception plan in the past 1 years.
3. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment.
4. Uncontrolled infectious disease within 4 weeks prior to enrollment.
5. Active hepatitis B/C virus.
6. HIV infected patients.
7. Suffering from a serious autoimmune disease or immunodeficiency disease.
8. The patient is allergic and is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
9. The patient participated in other clinical trials within 6 weeks prior to enrollment.
10. Systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
11. Have a history of epilepsy or other central nervous system diseases.
12. Having drug abuse/addiction.
13. According to the researcher's judgment, the patient has other unsuitable grouping conditions.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 3 years
Secondary outcomes:
measure: One-month remission rate
timeFrame: 1 month
measure: Overall survival
timeFrame: 3 years
measure: Event-free survival
timeFrame: 3 years
measure: Relapse-free survival
timeFrame: 3 years
measure: Quantity of anti-CD30 CAR-T cells in bone marrow cells and peripheral blood cells
timeFrame: 3 years
measure: Quantity of anti-CD30 CAR copies in bone marrow cells and peripheral blood cells
timeFrame: 3 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Heng Mei, M.D. Ph.D
role: PRINCIPAL_INVESTIGATOR
References: