Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies

Hodgkin Lymphoma Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04008394
• Other study ID #: WHUH-CART-CD30-01
• Status: Recruiting
• Phase: Phase 1
• Start date: July 3, 2019
• Est. completion date: January 1, 2023

Study information

• Verified date: August 2019
• Source: Wuhan Union Hospital, China
• Contact: Yu Hu, M.D. Ph.D
• Phone: 86-13986183871
• Email: dr_huyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 1, 2023
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adult T-Cell Lymphoma/Leukaemia
• Anaplastic Large Cell Lymphoma
• Angioimmunoblastic T-cell Lymphoma
• Hodgkin Disease
• Hodgkin Lymphoma
• Leukemia-Lymphoma, Adult T-Cell
• Lymphoma
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Neoplasms
• NK/T-cell Lymphoma
• Peripheral T Cell Lymphoma

Intervention

Genetic:
• Anti-CD30 CAR T cells
Patients receive CD30 CAR-T cells transduced with a lentiviral vector on day 0 in the absence of disease progression or unacceptable toxicity. Autologous 3th generation anti-CD30 CAR T cells.

Locations

Country	Name	City	State
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (2)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China	Wuhan Bio-Raid Biotechnology Co, Ltd. China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events	Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).	3 years
Secondary	One-month remission rate	Response to CAR-T therapy was assessed on day 30 (±2), against the National Comprehensive Cancer Network (NCCN, Version 1.2015).	1 month
Secondary	Overall survival	OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).	3 years
Secondary	Event-free survival	EFS was calculated from the first CAR-T cell infusion to death, progression of the disease, relapse or gene recurrence, whichever came first, or last visit (censored).	3 years
Secondary	Relapse-free survival	RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).	3 years
Secondary	Quantity of anti-CD30 CAR-T cells in bone marrow cells and peripheral blood cells	In vivo (bone marrow and peripheral blood) quantity of CAR-T cells were determined by means of flow cytometry.	3 years
Secondary	Quantity of anti-CD30 CAR copies in bone marrow cells and peripheral blood cells	In vivo (bone marrow and peripheral blood) quantity of anti-CD30 CAR copies were determined by means of qPCR.	3 years