B-cell Acute Lymphoblastic Leukemia
Conditions
Keywords
B-ALL, Allogenic CAR-γδT Cell, CD19, cell therapy
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALQH103 Cell Injection
dose escalation (3+3) : dose 1 (3×10\^8CAR+cells) ,dose 2 (1 × 10\^9 CAR+cells）,dose 3 (3 × 10\^9CAR+cells)
DRUGFludarabine
Intravenous fludarabine on days-5\ -2,the infusion dose is adjusted according to the subject's condition
DRUGCyclophosphamide
Intravenous cyclophosphamide on days -5\ -3, the infusion dose is adjusted according to the subject's condition
Sponsors
Anhui Provincial Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥14 years, gender is not limited; 2. Patients with clinically diagnosed relapsed/refractory B-ALL (except those presenting with extramedullary disease only), including any of the following: 1. Failure to obtain CR after 2 cycles of standard chemotherapy; 2. First induction of CR, but duration of CR is ≤12 months; 3. Relapsed/refractory B-ALL that has failed to respond to the first or multiple salvage treatments; 4. Relapse after hematopoietic stem cell transplantation, including hematological relapse and positive micro residual disease (MRD). 3. Cytological or histological confirmation of tumor cell immunophenotyping as CD19 positive; 4. Bone marrow with a ratio of ≥5% primitive/naïve lymphocytes (morphology); 5. Expected survival time of more than 3 months; 6. Eastern Cooperative Oncology Group (ECOG) score of 0-2; 7. Vital organ function meets the following requirements: left ventricular ejection fraction ≥50% on echocardiography; serum creatinine≤1.5 × upper limit of normal range (ULN); glutamine aminotransferase, aspartate aminotransferase ≤3 times ULN, total bilirubin ≤1.5 times ULN; 8. Pregnancy tests for women of childbearing age should be negative, and both men and women should agree to use effective contraception during treatment and for the following 1 year. 9. Toxicity of prior antitumor therapy ≤ grade 1 (according to CTCAE version 5.0) or acceptable inclusion/
Exclusion criteria
level. 10. No significant hereditary disease; 11. Be able to understand the requirements and matters of the trial and be willing to participate in the clinical study as required; 12. Sign the trial informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) | 12 months | 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 |
| Incidence of Dose-Limiting Toxicities (DLTs) | First infusion date of QH103 cells to 28 days end cell infusion | 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. |
| Maximum tolerated dose (MTD) | 28 days | MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS） | 12 months | 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. |
| Progression Free Survival (PFS) | 12 months | 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. |
| Pharmacokinetics: Persistence of the QH103 cells | 28 days | Persistence of the QH103 cells assessed by number in peripheral blood. |
| Pharmacodynamics: Peak level of cytokines in serum | 28 days | 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. |
| Overall Response Rate(ORR) | 12 months | Proportion of subjects with CR (complete response) and CRi (complete response with incomplete hemocyte recovery) |
Countries
China
Contacts
Primary ContactXiaoyu Zhu, Ph.D
Backup ContactGuangyu Sun
Outcome results
None listed