PA3-17 Injection Treatment of Adult Patients With CD7-positive Relapsed/Refractory Lymphoid Hematologic Malignancies

NCT05170568 | Unknown Phase 1

• 1 other identifier: PG-CART-07-001 (1)
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I, open-label, dose-escalation clinical study with the primary objective of evaluating the safety and tolerability of PA3-17 injection in adult subjects with CD7-positive relapsed/refractory lymphoid hematologic malignancies. The secondary objectives are as follows: to evaluate the proliferation and in vivo persistence of CD7-targeted chimeric antigen receptor T (CAR-T) cells after injection of PA3-17; to evaluate the proportion of CD7-positive cells in peripheral blood after injection of PA3-17; to preliminarily evaluate the efficacy of PA3-17 injection in adult subjects with CD7-positive relapsed/refractory lymphoid hematologic malignancies; to evaluate the immunogenicity of PA3-17 injection; and to explore the applicable dose in Phase II trial.

Conditions

CD7-positive Relapsed/Refractory Lymphoid Hematologic Malignancies

Outcome Measures

Primary Outcomes (2)

• DLT

  Dose limiting toxicity

  About 2 years

• MTD

  Maximum tolerated dose

  About 2 years

Secondary Outcomes (13)

• Assessment of the safety after CD7-targeted chimeric antigen receptor T cells infusion (Safety)

  About 2 years

• Assessment of pharmacokinetic (about Cmax)

  28 days

• Assessment of pharmacokinetic (about Tmax)

  28 days

• Assessment of pharmacokinetic (about AUC0-28d)

  28 days

• Assessment of pharmacokinetic (about Cmax)

  90 days

Study Arms (1)

T cell injection targeting CD7 chimeric antigen receptor

EXPERIMENTAL

Biological: T cell injection targeting CD7 chimeric antigen receptor

Interventions

T cell injection targeting CD7 chimeric antigen receptor BIOLOGICAL

The subjects, who sign the informed consent forms and been screened by inclusion/exclusion criteria, will be assigned into 0.5 × 106, 2.0 × 106 and 4.0 × 106 CAR-T/kg groups in order of sequence. And the subjects will be administered once.

Also known as: PA3-17 injection

T cell injection targeting CD7 chimeric antigen receptor

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 70 years old (inclusive), male or female;
• Expected survival time ≥ 3 months;
• ECOG performance status of 0-1;
• Malignant lymphoma diagnosed according to WHO2016 criteria: priority will be given to T-cell acute lymphoblastic leukemia/lymphoma (including early pre-T-cell lymphoblastic leukemia);
• Subjects with recurrent/refractory T-cell acute lymphoblastic leukemia/lymphoma (including early pre-T-cell lymphoblastic leukemia) who have failed standard treatment or lack effective treatment and meet any of the following criteria:
• No remission after at least two courses of standard induction chemotherapy;
• Early relapse (\<12 months) after complete remission; Or complete remission followed by late relapse (≥12 months) without remission after a course of standard induction chemotherapy;
• Patients who did not achieve remission after two or more lines of chemotherapy;
• Recurrence after hematopoietic stem cell transplantation.
• Lymphoid hematologic malignancies diagnosed as CD7 positive by flow cytometry and/or CD7 positive by histopathological immunohistochemistry at screening, with the positive rate of tumor ≥ 30%;
• For CD7-positive lymphoid hematologic malignancies involving bone marrow and/or peripheral blood, patients with CD4/CD8 double-negative surface immunophenotype of tumor cells as determined by flow cytometry;
• Liver, kidney and cardiopulmonary function shall meet the following requirements:
• Creatinine ≤ 1.5 ULN;
• Left ventricular ejection fraction ≥ 45%;
• Oxygen saturation \> 91%;

You may not qualify if:

• Subjects who need to use immunosuppressants;
• Subjects with malignant tumors other than T-cell hematological malignancies within 5 years prior to screening, with the exception of adequately treated cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinoma, localized prostate cancer after radical surgery, and ductal carcinoma in situ after radical mastectomy;
• Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA titer detection not within the normal reference range; positive for hepatitis C virus (HCV) antibody and peripheral blood hepatitis C virus (HCV) RNA; positive for human immunodeficiency virus (HIV) antibody; positive for cytomegalovirus (CMV) DNA test; positive for syphilis test;
• Severe heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association \[NYHA\] classification ≥ III), severe arrhythmia;
• Unstable systemic diseases judged by the investigator: including but not limited to serious liver, kidney or metabolic diseases requiring drug treatment;
• Within 7 days prior to screening, there are active or uncontrollable infections requiring systemic therapy (except for mild genitourinary infection and upper respiratory tract infection);
• Pregnant or lactating women, and female subjects who plan to become pregnant within 2 years after cell infusion or male subjects whose partners plan to become pregnant within 2 years after cell infusion;
• Subjects who have received CAR-T therapy or other gene-modified cell therapy prior to screening;
• Subjects who are receiving systemic steroid therapy within 7 days prior to screening or need long-term use of systemic steroid therapy during treatment as judged by the investigator (except for inhalation or topical use);
• Subjects who have participated in other clinical studies within 3 months prior to screening;
• Subjects who have evidence of central nervous system invasion at screening;
• Conditions not eligible for cell preparation as judged by the investigator;
• Other conditions considered unsuitable for enrollment by the investigator.

Sponsors & Collaborators

• PersonGen BioTherapeutics (Suzhou) Co., Ltd.: lead
• The First Affiliated Hospital of Zhengzhou University: collaborator
• Peking University People's Hospital: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• Hematology Hospital of Chinese Academy of Medical Sciences (Hematology Research Center of Chinese Academy of Medical Sciences): collaborator
• Zhejiang University: collaborator

Study Sites (1)

PersonGen.Anke Cellular Therapeutice Co., Ltd.

Hefei, Anhui, 230088, China

RECRUITING

Study Officials

• Mingzhi Zhang, Doctor

  The First Affiliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

• Xiaojun Huang, Doctor

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

• Heng Mei, Doctor

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

• Dehui Zou, Doctor

  Hematology Hospital of Chinese Academy of Medical Sciences (Hematology Research Center of Chinese Academy of Medical Sciences)

  PRINCIPAL INVESTIGATOR

• He Huang, Doctor

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mingzhi Zhang, Doctor

CONTACT

037166295562; mingzhi_zhang@126.com

Xiaojun Huang, Doctor

CONTACT

+86-13701389625; xjhrm@medmail.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: PA3-17 injection

Study Record Dates

• First Submitted: December 24, 2021
• First Posted: December 28, 2021
• Study Start: December 1, 2021
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2024
• Last Updated: November 1, 2022

Record last verified: 2022-10

Locations

CN (1)