CD7 CAR-T Cells for Patients With R/R CD7+ NK/T Cell Lymphoma,T-lymphoblastic Lymphoma and Acute Lymphocytic Leukemia

CD7 CAR-T Cells for Patients With Relapse/Refractory CD7+ NK/T Cell Lymphoma ,T-lymphoblastic Lymphoma and Acute Lymphocytic Leukemia

This study is designed to explore the safety and efficacy of CD7 CAR-T Cells for patients with relapse/refractory CD7+ NK/T cell lymphoma ,T-lymphoblastic lymphoma and Acute Lymphocytic Leukemia. And to evaluate the pharmacokinetics of CD7 CAR-T cells in patients.

Study Overview

• Status: Unknown
• Conditions: Acute Lymphocytic Leukemia; T-lymphoblastic Lymphoma; NK/T Cell Lymphoma
• Intervention / Treatment: Drug: CD7 CAR-T cells infusion

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • First Affiliated Hospital of Zhengzhou University
      • Contact: Min Yao, Bachelor's; Phone Number: +8618355313511; Email: 1248135168@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 68 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Aged 7 to 70 years.

  2. The expected survival period is more than 12 weeks.

  3. ECOG: 0-2.

  4. Male and female subjects with CD7+ NK/T cell lymphoma ,T-lymphoblastic lymphoma and Acute Lymphocytic Leukemia in patients with no available curative treatment options will be enrolled:

  1. Not achieved PR after the standard first-line treatment for at least 4 courses.
  2. Relapse or progression after standardized treatment.
  3. Patients With NK/T Cell Lymphoma or T-lymphoblastic Lymphoma need to have at least 1 tumor lesions can be evaluated.

  5. Cardiac left ventricle ejection fraction ≥40%.

  6. Serum creatinine≤1.5 ULN; oxygen saturation of blood >91%.

  7. Total bilirubin≤1.5×ULN; Serum ALT and AST≤2.5 ULN.

  8. Able to understand this study and have signed informed consent.

Exclusion Criteria:

• 1. Patients with graft-versus-host disease (GVHD) or who need to use immunosuppressive drugs.

  2. Patients with malignant tumors other than NK/T cell lymphoma , T-lymphoblastic lymphoma and Acute Lymphocytic Leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer, local prostate after radical surgery, breast ductal carcinoma in situ after cancer and radical surgery.

  3. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is not within the normal range; hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C Viral (HCV) RNA positive; human immunodeficiency virus (HIV) antibody positive; cytomegalovirus (CMV) DNA positive; syphilis positive.

  4. Severe heart disease: including but not limited to unstable angina pectoris, myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ III), severe arrhythmia.

  5. Unstable systemic diseases judged by investigator, including but not limited to severe liver, kidney or metabolic diseases needing medical treatment.

  6. Active or uncontrollable infections (except for mild genitourinary infections and upper respiratory tract infections) that require systemic treatment within 7 days prior to screening; 7. Women who are pregnant or breastfeeding, female subject who plans to have a pregnancy within 1 year after cell infusion, and male subject who plans to have a pregnancy within 1 year after cell infusion.

  8. Subject who have received CAR-T treatment or other genetically modified cell therapy before screening; 9. Subjects who are receiving systemic steroid therapy within 7 days prior to screening or who require long-term systemic steroid therapy judged by investigator (except for inhaled or topical use); 10. Participated in other clinical studies within 3 months prior to screening. 11. Patients with active CNS involvement by malignancy. 12. Not suitable for cell preparation. 13. Researchers consider it inappropriate to participate in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CD7 CAR-T cells Infusion

Drug: CD7 CAR-T cells infusion; Biological: CD7 CAR-T cells infusion. Pretreatment: patients enrolled in this study will receive cyclophosphamide or fludarabine plus cyclophosphamide. CD7 CAR-T cells infusion are allowed within 2 weeks after treatment. CD7 CAR-T cells infusion: 30-60 minutes before infusion, H1 anti-histamine agents are applied (acetaminophen 30mg,po.; promethazine 25mg,i.v. ; diphenhydramine 0.5-1mg/kg, no more than 50mg.). Non-physiological doses of corticosteroids are not applied for patients during treatment or recovery unless a life-threatening emergency occurs. CD7 CAR-T cells are infused into patients for one or two times, the number of infused CD7 CAR-T cells are 0.5-5×10^6/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of the dose limiting toxicity (DLT)	Toxicity will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale, version 5 and the number of patients experiencing DLT will be evaluated.	Time Frame: 4 weeks after CAR T cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		Up to 2 years
Disease-free survival		Up to 2 years
In vivo persistence/expansion of infused CAR T cell	Detection of infused CAR T cell in the peripheral blood.	Up to 2 years
Determine the effects of CART-CD7 infusion on T cells and CD7 expression in vivo.		Up to 2 years
Overall Response Rate (ORR)		4 weeks after CAR T cell infusion

Collaborators and Investigators

• Sponsor: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Collaborators: The First Affiliated Hospital of Zhengzhou University

Publications and helpful links

General Publications

• Zhang M, Chen D, Fu X, Meng H, Nan F, Sun Z, Yu H, Zhang L, Li L, Li X, Wang X, Wang M, You F, Li Z, Chang Y, Zhou Z, Yan J, Li J, Wu X, Wang Y, Wang Y, Xiang S, Chen Y, Pan G, Xu H, Zhang B, Yang L. Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma. Clin Cancer Res. 2022 Jul 1;28(13):2830-2843. doi: 10.1158/1078-0432.CCR-21-4097.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2019
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: June 28, 2019
• First Submitted That Met QC Criteria: June 28, 2019
• First Posted (Actual): July 2, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2020
• Last Update Submitted That Met QC Criteria: September 25, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Acute Lymphocytic Leukemia; NK/T cell lymphoma; T-lymphoblastic lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
• Other Study ID Numbers: PG-CART-007-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No