QH101 Cell Therapy Relapsed/Refractory(R/R) Acute Myeloid Leukemia(AML) and Myelodysplastic Syndromes(MDS)

NCT07131085 | Not Yet Recruiting Phase 1

• 1 other identifier: QH10104-RML-01（0）
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

MDS; AML

Keywords

TCR; BTN; γδT; allogeneic; cell therapy

Outcome Measures

Primary Outcomes (2)

• 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.

  12 months

• Incidence of dose-limiting toxicity (DLT)

  Within 28 days post-cell infusion

Secondary Outcomes (4)

• Pharmacokinetics: Persistence of QH101

  12 months

• Overall response rate (ORR)

  12 months

• Immunogenicity: Proportion of subjects with anti drug antibody (ADA)

  12 months

• Pharmacodynamics: Peak level of cytokines in serum

  Up to 28 days after infusion

Study Arms (1)

Patients with R/R AML or MDS

EXPERIMENTAL

Patients with R/R AML or MDS. A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, QH101 product.

Drug: Allogeneic TCR-enhanced γδ T cell(QH101); Drug: Fludarabine (FLU); Drug: Cyclophosphamide (CTX)

Interventions

Allogeneic TCR-enhanced γδ T cell(QH101) DRUG

dose 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)

Patients with R/R AML or MDS

Fludarabine (FLU) DRUG

Intravenous fludarabine 20\~30 mg/m\^2/day on days -5, -4, and -3

Patients with R/R AML or MDS

Cyclophosphamide (CTX) DRUG

Intravenous cyclophosphamide 300\~500 mg/m\^2/day on days -5, -4, and -3.

Patients with R/R AML or MDS

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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;
• Presence of severe autoimmune diseases or immunodeficiency disorders;
• Presence of active graft-versus-host disease requiring ongoing systemic treatment;
• Subjects currently receiving systemic steroid or other immunosuppressive therapy prior to screening, and who are determined by the investigator to require long-term use of such therapy after enrollment (excluding inhaled or topical use);
• Other severe medical conditions deemed inappropriate for enrollment by the investigator (e.g., uncontrolled hypertension or diabetes, severe renal insufficiency, severe pulmonary dysfunction, etc.);
• Active HBV or HCV infection (HBV-DNA positive or HCV-RNA positive), HIV-positive, or positive syphilis test results;
• Other severe or persistent active infections;
• Adverse events related to systemic immunotherapy (including other investigational drugs or medical device interventions) prior to screening have not yet decreased to Grade 1 severity or returned to baseline status;
• Discontinuation of immunosuppressive agents for less than 2 weeks;
• History of allergy to any component of the cellular product;
• Vaccination or any surgical procedure within 4 weeks prior to screening;
• Other conditions deemed by the investigator to potentially increase the risk to the subject or interfere with trial results.

Sponsors & Collaborators

• Anhui Provincial Hospital: lead

MeSH Terms

Interventions

fludarabine; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Xiaoyu Zhu

CONTACT

15255456091; xiaoyuz@ustc.edu.cn

Guangyu Sun

CONTACT

13956970687; sunguangyu_vip@foxmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hematology Department

Study Record Dates

• First Submitted: August 5, 2025
• First Posted: August 20, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 20, 2025

Record last verified: 2025-08