CD70-CAR-NK Cell Therapy for T Cell Lymphoma and Acute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorSecond Affiliated Hospital, School of Medicine, Zhejiang University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Design model
Single group
Treatments tested in this trial
CD70 CAR-NK
Biological/VaccineCAR - 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.
Treatment groups
25 Participants
are divided into 1 treatment groupGroup A: CD70 CAR-NK for the treatment of CD70-positive relapsed/refractory T-cell lymphoma and AMLExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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
Time frame
28 days2
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
Time frame
within 90 days after CAR-NK infusionSecondary outcomes
1
Objective response rate (ORR) at day 30
To evaluate the overall response rate (PR+CR )as assessed by PET-CT for T cell lymphoma, and by bone marrow examination for AML
Time frame
30 days2
duration of response
duration of response measured as the time from the date of first documentation of response to the date of first documented progression
Time frame
2 years3
progression-free survival
defined as the time from the date of randomization to the date of first documentation of disease progression based on NCCN criteria as evaluated by an independent review committee (IRC), or death due to any cause, whichever occurs first.
Time frame
2 yearsOther outcomes
1
CAR copies as assessed by qPCR
CAR copies in peripheral blood will be monitored by qPCR within 6 months
Time frame
6 months2
phenotypes of CAR-NK cells as assessed by flow cytometry
the proportions of CAN-NK cells with different immunophenotypes
Time frame
1 yearSponsors and contacts
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Source ClinicalTrials.gov