About this trial
QH101 is an allogeneic TCR-enhanced Vδ2 T cell therapy product engineered to express BTN protein-specific binding elements on the cell surface. This innovative approach harnesses the natural cytotoxic capabilities of Vδ2 T cells while augmenting their ability to recognize BTN proteins, thereby significantly improving tumor cell elimination efficiency. Notably, QH101 is designed without co-stimulatory signal domains or the CD3ζ domain, which prevents T cell exhaustion from overactivation and effectively enhances in vivo persistence.
Patients with R/R AML face particularly poor prognoses, with conventional chemotherapy and targeted therapies achieving suboptimal complete remission rates and long-term survival below 10%. Similarly, R/R MDS patients typically demonstrate median overall survival of less than one year (with TP53-mutated cases showing even poorer outcomes of 3-6 months), making clinical trial participation the most viable therapeutic option.
The development of effective treatments for R/R AML/MDS presents significant challenges due to:1)The paucity of disease-specific molecular targets;2)The slow progress in drug development. Allogeneic γδ T-cell therapy featuring enhanced TCR functionality and multi-mechanism tumoricidal activity represents a promising investigational approach for addressing R/R AMLMDS. This innovative strategy combines the advantages of: 1)Improved target recognition through TCR enhancement; 2)Multi-faceted tumor-killing mechanisms; 3)Potential for better safety and persistence profiles.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 14 years, no gender restrictions;
Relapsed: Leukemic cells reappear in the peripheral blood after complete remission, or Leukemic blasts≥5% in the bone marrow (excluding other causes such as bone marrow regeneration after consolidation chemotherapy), or leukemic cell infiltration in extramedullary sites;
Relapsed: Patients who have achieved hematologic improvement or CR but subsequently experience hematologic decline (e.g., hemoglobin <10 g/dL, platelets <50×10⁹/L, neutrophils <1.0×10⁹/L), or an increase in the proportion of blast cells in the bone marrow (≥5%), or the emergence of new cytogenetic abnormalities or molecular progression (e.g., increased TP53 mutation burden);
Refractory: No hematologic or bone marrow improvement after ≥4-6 cycles of hypomethylating agent (HMA) therapy (e.g., azacitidine or decitabine), or low-risk MDS resistant to erythropoietin or immunomodulatory agents (e.g., lenalidomide).
Disqualifiers
Patients with a history of severe central nervous system disorders, such as uncontrolled epileptic seizures, stroke, severe brain injury with aphasia, paralysis, dementia, Parkinson's disease, or mental disorders;
New York Heart Association (NYHA) Class III or IV heart failure;
Undergone coronary angioplasty, coronary stent implantation, or coronary artery bypass surgery; or experienced thrombotic or embolic events (e.g., cerebrovascular events [including transient ischemic attacks, but excluding lacunar cerebral infarction], deep vein thrombosis [excluding deep vein thrombosis caused by PICC catheter placement], pulmonary embolism, etc.);
Presence of disseminated intravascular coagulation;
Trial design
Single group
Treatments tested in this trial
Allogeneic TCR-enhanced γδ T cell(QH101)
Drugdose escalation (3+3) : dose 1 (5×10\^8 enTCR γδ cells) , dose 2 (1.5×10\^9 enTCR γδ cells), dose 3 (3×10\^9 enTCR γδ cells)
Fludarabine (FLU)
DrugIntravenous fludarabine 20\~30 mg/m\^2/day on days -5, -4, and -3
Cyclophosphamide (CTX)
DrugIntravenous cyclophosphamide 300\~500 mg/m\^2/day on days -5, -4, and -3.
Treatment groups
Trial outcomes
Primary outcomes
Incidence of AE
AE is defined as any adverse medical event occurring from the date of lymphocyte depletion to 12 months after QH101 infusion. Among these, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) are graded according to the standards set by the American Society for Transplantation and Cellular Therapy (ASTCT). Graft-versus-host disease (GVHD) is graded according to the standards defined by the Mount Sinai Acute GVHD International Consortium. Other AEs are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Incidence of dose-limiting toxicity (DLT)
Secondary outcomes
Pharmacokinetics: Persistence of QH101
Persistence of QH101 assessed by number in peripheral blood.
Overall response rate (ORR)
The proportion of subjects achieving CR (complete remission)/CRh (complete remission with partial hematological recovery)/CRi (complete remission with incomplete hematological recovery)/PR (partial remission)
Immunogenicity: Proportion of subjects with anti drug antibody (ADA)
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), interferon-γ(IFN-γ). Peak was defined as the maximum post-baseline level of the cytokine.
Locations
Sponsors and contacts
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