CD70-CAR-NK Cell Therapy for T Cell Lymphoma and Acute Myeloid Leukemia

NCT06696846 | Recruiting Phase 1 DMC

• 1 other identifier: 2024-0992
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

CD70 is a promising target for immunotherapy because it is overexpressed in T-cell lymphoma (TCL) and acute myeloid leukemia (AML) tumor cells but is found in deficient levels in normal tissues and hematopoietic stem cells. This study aims to evaluate the safety and efficacy of CD70-targeted CAR-NK (CD70-CAR-NK) cells in patients with relapsed and refractory TCL and AML.

Conditions

Relapsed/Refractory T-cell Lymphoma; Relapsed/Refractory Acute Myeloid Leukemia

Keywords

CD70; CAR-NK; T cell lymphoma; acute myeloid leukemia

Outcome Measures

Primary Outcomes (2)

• The incidence and type of dose-limiting toxicity (DLT) within 28 days

  To determine the incidence and type of dose-limiting toxicity (DLT) within 28 days after CD70-CAR - NK cell infusion

  28 days

• the incidence and severity of treatment-related adverse events as assessed by CTCAE v4.0

  CAR-NK treatment-related AEs include CRS, ICANS, cytopenia, and other non-hematological toxicities

  within 90 days after CAR-NK infusion

Secondary Outcomes (3)

• Objective response rate (ORR) at day 30

  30 days

• duration of response

  2 years

• progression-free survival

  2 years

Other Outcomes (2)

• CAR copies as assessed by qPCR

  6 months

• phenotypes of CAR-NK cells as assessed by flow cytometry

  1 year

Study Arms (1)

CD70 CAR-NK for the treatment of CD70-positive relapsed/refractory T-cell lymphoma and AML

EXPERIMENTAL

The first stage is a dose escalation study, with three CD70 CAR-NK dose levels. Each dose level is planned to recruit 3 to 6 subjects to evaluate safety and efficacy and determine the number of CD70 CAR-NK cells for treatment in the second stage. The second stage is the dose expansion stage, where 30 subjects are recruited to receive the number of CD70 CAR-NK cells recommended in the first stage.

Biological: CD70 CAR-NK

Interventions

CD70 CAR-NK BIOLOGICAL

CAR - NK cells constructed by using genetic engineering technology retain the original extensive tumor - killing ability of NK cells. By using their unique target cell recognition mechanism, the target is accurately locked on specific antigen proteins, thereby enhancing the anti - tumor effect. Cord blood-derived CAR - NK cell products shorten the treatment time and are inexpensive. Multiple studies have confirmed the feasibility of CAR - NK cells in treating hematological tumors. Blocking the CD70/CD27 signaling pathway plays an important role in inhibiting CD70 - positive tumors, such as refractory/relapsed T - cell lymphoma and acute myeloid leukemia. Pre - clinical studies in our laboratory have proved that CD70 CAR - NK can effectively inhibit the in - vivo and in - vitro proliferation of T - cell lymphoma and prolong survival.

CD70 CAR-NK for the treatment of CD70-positive relapsed/refractory T-cell lymphoma and AML

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• According to the WHO disease classification, patients with relapsed/refractory T - lymphoma and acute myeloid leukemia:
• Voluntarily participate in this study and sign the informed consent form;
• Aged between 18-75 years old, both male and female are eligible;
• Relapsed/refractory T cell lymphoma is defined as: relapsed/refractory after having received at least two or more lines of previous treatment (patients with anaplastic large -cell lymphoma must have been exposed and resistant to Brentuximab vedotin). The celluar subtypes of T-cell lymphoma include: angioimmunoblastic T-cell lymphoma; peripheral T - cell lymphoma not otherwise specified; ALK-negative anaplastic large - cell lymphoma; Relapsed/refractory AML is defined as: leukemia cells reappear in the peripheral blood after complete remission or the blasts in the bone marrow ≥ 5% or the extramedullary leukemia infiltration outside. Or newly diagnosed cases did not achieve a CR after two courses of standard regimens; those who relapse within 12 months after CR after consolidation and intensification treatment; those who relapse after 12 months and have not responded to conventional chemotherapy; those who relapse two or more times; those with persistent extramedullary leukemia;
• The expected survival period ≥ 12 weeks;
• CD70 expression is positive in tumor tissue puncture sections/tumor cells detected by flow cytometry, and the number of CD70 - positive cells detected by immunohistochemistry ≥ 20% (++ or more);
• ECOG score is 0 - 2;
• Adequate organ function reserve:
• Alanine aminotransferase and aspartate aminotransferase ≤ 2.5× UNL;
• Creatinine clearance rate (Cockcroft - Gault method) ≥ 60 mL/min;
• Serum total bilirubin and alkaline phosphatase ≤ 1.5× UNL;
• Glomerular filtration rate \> 50 ml/min;
• Cardiac ejection fraction ≥ 45%;
• Under indoor natural air environment, the basic oxygen saturation \> 92%;
• Routine blood test: absolute neutrophil count \> 1000/mm3, platelet count ≥ 45×109, hemoglobin ≥ 8.0g/dl (the standard for AML patients is ≥ 7.0g/dl; blood transfusion is allowed);

You may not qualify if:

• Subjects meeting any of the following criteria will not be eligible for this study:
• Those with a history of allergy to any component in the cellular product;
• Those with a history of other tumors;
• Those who had grade II - IV (Glucksberg criteria) acute GvHD or extensive chronic GvHD after previous allogeneic hematopoietic stem cell transplantation; or those who are currently receiving anti - GvHD treatment;
• Those who have received gene therapy within the past 3 months;
• Those with active infections requiring treatment (except for simple urinary tract infections and bacterial pharyngitis). However, prophylactic antibiotic, antiviral, and antifungal treatments are permitted;
• Subjects with grade III or IV cardiac insufficiency according to the New York Heart Association cardiac function classification standard of the United States;
• Those whose toxic reactions from previous anti - tumor treatment have not recovered (CTCAE 5.0 toxic reactions have not recovered to ≤ grade 1, except for fatigue, anorexia, and alopecia);
• Subjects with a history of epilepsy or other central nervous system diseases;
• Lactating women who are unwilling to stop breastfeeding;
• Any other circumstances that, in the opinion of the investigator, may increase the risk to the subject or interfere with the test results;
• Those with positive nucleic acid tests for COVID - 19 or influenza A.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, T-Cell; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Hematologic Diseases

Central Study Contacts

Wenbin Qian

CONTACT

+86 0571 87783759; qianwb@zju.edu.cn

Yang Xu, Ph.D

CONTACT

yxu@zju.edu.cn

Study Design

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

Study Record Dates

• First Submitted: November 12, 2024
• First Posted: November 20, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)