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

Efficacy and Safety of Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies：a Single-center, Open, Single-arm Clinical Study.

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.

Study Overview

• Status: Unknown
• Conditions: Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Peripheral T Cell Lymphoma; NK/T-cell Lymphoma; Adult T-Cell Lymphoma/Leukaemia
• Intervention / Treatment: Genetic: Anti-CD30 CAR T cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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
EXPERIMENTAL: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Overall survival	OS was calculated from the first CAR-T cell infusion to death or last follow-up (censored).	3 years
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
Relapse-free survival	RFS was calculated from the first CAR-T cell infusion to relapse or last visit (censored).	3 years
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
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

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Collaborators: Wuhan Bio-Raid Biotechnology Co, Ltd. China

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 3, 2019
• Primary Completion (ANTICIPATED): July 1, 2022
• Study Completion (ANTICIPATED): January 1, 2023

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 2, 2019
• First Posted (ACTUAL): July 5, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 7, 2019
• Last Update Submitted That Met QC Criteria: August 5, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Refractory/Relapsed; CD-30 CART; lymphocyte malignancies
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia; Lymphadenopathy; Leukemia, T-Cell; Neoplasms; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Leukemia-Lymphoma, Adult T-Cell; Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy
• Other Study ID Numbers: WHUH-CART-CD30-01

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
• product manufactured in and exported from the U.S.: No