To evaluate the safety and tolerability of RC1012 infusion in patients with relapsed or refractory Acute Myelocytic Leukemia (r/r AML).
This study aims to evaluate the safety and tolerability of RC1012 injection in patients with relapsed or refractory Acute Myelocytic Leukemia (r/r AML). DNT cells are mature T lymphocytes that comprise 3-10% of T cells in human peripheral blood mononuclear cells (PBMC). Allo-DNT cells from healthy donors have been proved to be safe and demonstrated potent cytotoxicity against AML blasts from AML patients in preclinical and preliminary clinical studies. Allo-DNT cells will be collected from healthy donors (NO MHC match needed) and infused into patients. The drug for this study is an off-the-shelf product. Patients DO NOT need to wait for the cell manufacturing.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
RC1012 injection (allo-DNT cells) from healthy donors and have been proved to be safe and demonstrated potent cytotoxicity against AML blasts from AML patients in preclinical and preliminary clinical studies. Allo- DNT cells will be collected from healthy donors (NO MHC match needed) and injected into patients. The drug for this study is an off-the-shelf product. Patients DO NOT need to wait for the cell manufacturing.
First Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, China
RECRUITINGDose-Limiting Toxicity (DLT)
To evaluate the safety, tolerability, and determine the recommended dosage of allo-DNT Cell Therapy for Relapsed/Refractory Acute Myelocytic Leukemia
Time frame: Up to 28 days
Maximum Tolerated Dose (MTD)
MTD was the highest dose for DLT in ≤1/6 subjects
Time frame: Up to 28 days
Incidence of abnormalities
Incidence of abnormalities in AE/SAE/laboratory tests/electrocardiograms/vital signs.
Time frame: Up to 28 days
Pharmacokinetics (PK) indicator (Cmax)
The peak concentration of allo-DNT cells amplified in the peripheral blood (Cmax, detected by Flow Cytometry).
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (AUC)
Allo-DNT cells blood concentrations will be measured at different time points to evaluate the area under the curve (AUC). (AUC, detected by Flow Cytometry).
Time frame: Up to 2 years
Pharmacokinetics (PK) indicator (Tmax)
Allo-DNT cells blood concentrations will be measured at different time points to evaluate the peak time (Tmax) in peripheral blood. Tmax is defined as the time to reach the highest concentration (Tmax, detected by Flow Cytometry).
Time frame: Up to 2 years
Pharmacokinetics (PK) indicator (T1/2)
Allo-DNT cells blood concentrations will be measured at different time points to evaluate the elimination half-life in hours (T1/2). T1/2 is defined as the time point when the concentration of allo-DNT reaches half of maximum in a patient's peripheral blood (T1/2, detected by Flow Cytometry).
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Time frame: Up to 2 years
Overall Response Rate
ORR includes complete response (CR), CRi and PR. CR was defined as \< 5% bone marrow blasts in an aspirate with spicules, no blasts with Auer rods or persistence of extramedullary disease, and independent of transfusions; CRi: was defined as\<5% bone marrow blasts, either ANC\<1×10\^9/L or platelets\<100×10\^9/L, transfusion independence but with persistence of cytopenia; PR was defined as decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow aspirate and the normalization of blood counts.
Time frame: Up to 2 years
Event-Free Survival
From the date of enrollment in the clinical trial until the failure of treatment, relapse or death.
Time frame: Up to 2 years
Duration of Response
The time from the start of the first assessment of CR or PR to the first assessment as disease recurrence or progression or death
Time frame: Up to 2 years
Relapse-Free Survival
Relapse-free survival is the time from study enrollment until documented disease relapse, or death from any cause.
Time frame: Up to 2 years
Overall Survival
From the date of entry into the clinical study until death from any cause.
Time frame: Up to 5 years