This is a single-arm, single-center, interventional, dose-escalation clinical study designed to evaluate the safety and tolerability of QH103 Cell Injection in the treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia.
To evaluate the safety and tolerability of QH103 Cell Injection in the treatment of relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia, and to evaluate dose-limiting toxicity and maximum tolerated dose.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
dose escalation (3+3) : dose 1 (3×10\^8CAR+cells) ,dose 2 (1 × 10\^9 CAR+cells),dose 3 (3 × 10\^9CAR+cells)
Intravenous fludarabine on days-5\~-2,the infusion dose is adjusted according to the subject's condition
Intravenous cyclophosphamide on days -5\~-3, the infusion dose is adjusted according to the subject's condition
Anhui Provincial Hospital
Hefei, Anhui, China
RECRUITINGIncidence of Adverse Events (AEs)
AE is defined as any adverse medical event from the date of leukapheresis to 12 months after QH103 infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0
Time frame: 12 months
Incidence of Dose-Limiting Toxicities (DLTs)
DLT was defined as QH103 Cells-related events with onset within first 28 days following infusion: The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting \> 2 weeks; Any QH103 cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.
Time frame: First infusion date of QH103 cells to 28 days end cell infusion
Maximum tolerated dose (MTD)
MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.
Time frame: 28 days
Overall Survival (OS)
OS is defined as the time from QH103 cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
Time frame: 12 months
Progression Free Survival (PFS)
PFS is defined as the time from the QH103 cells infusion date to the date of disease progression assessed by investigators assessment, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
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Time frame: 12 months
Pharmacokinetics: Persistence of the QH103 cells
Persistence of the QH103 cells assessed by number in peripheral blood.
Time frame: 28 days
Pharmacodynamics: Peak level of cytokines in serum
The cytokines mainly include interleukin-2 (IL-2 ), IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α) etc. Peak was defined as the maximum post-baseline level of the cytokine.
Time frame: 28 days
Overall Response Rate(ORR)
Proportion of subjects with CR (complete response) and CRi (complete response with incomplete hemocyte recovery)
Time frame: 12 months