Injection of Allo-DNT Cells to Prevent Relapse in AML Patients After Transplant

A Phase I/II Clinical Trial of RC1012 Injection for the Prevention of Relapse in AML Patients After Allogeneic Hematopoietic Stem Cell Transplantation

This study is testing whether an injection of special immune cells can help prevent relapse in patients with Acute Myeloid Leukemia after they have had a stem cell transplant.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Guangdong Ruishun Biotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: tolimumab, chemotherapy
• Locations: 1 site (Hefei, Anhui)
• Trial ID: NCT05858814 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and tolerability of RC1012 injection, which contains allo-DNT cells, in patients with Acute Myeloid Leukemia (AML) who have recently undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The intervention involves infusing off-the-shelf allo-DNT cells collected from healthy donors, which do not require matching for MHC. The goal is to prevent relapse in high-risk AML patients by leveraging the cytotoxic properties of these mature T lymphocytes. The study is designed to assess the effectiveness of this approach in a Phase 1 and Phase 2 setting.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 diagnosed with AML who have received allo-HSCT within the last 60-100 days and exhibit high-risk factors for relapse.

Not a fit: Patients who do not meet the eligibility criteria, such as those outside the age range or without high-risk factors for relapse, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of relapse in AML patients after transplantation.

How similar studies have performed: Preliminary clinical studies have shown that allo-DNT cells are safe and effective against AML, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily sign an ICF and expect to complete the study procedures for follow-up examinations and treatment.
2. Aged 18 to 70 years (including cut-offs), regardless of gender.
3. Subject must be diagnosed with AML according to World Health Organization (WHO) criteria (2016).
4. The subject has received an allogeneic HSCT within 60-100 days, the percentage of malignant primitive cells in the bone marrow is \< 5% after HSCT and STR-PCR shows complete donor chimerism.
5. The subject has one of the following high-risk factors for relapse after allo-HSCT: (1) Failure to achieve remission after two courses of induction chemotherapy. (2) Prior history of Myelodysplastic Syndromes (MDS) or Myeloproliferative Neoplasm (MPN). (3) High leukocytes (≥100×10\^9/L) combined with Central Nervous System Leukemia (CNSL); (4) Positive Minimal Residual Disease (MRD) before HSCT; (5) Non-remission or disease progression prior to HSCT; (6) Subject with cytogenetic high-risk factors (except that who can be treated with targeted drugs).
6. The subject has recovered from the toxicity of the prior treatment, i.e., CTCAE toxicity grade \<2 (unless the abnormality is tumor-related).
7. ECOG score 0 to 1.
8. With appropriate organ function:

   * Glutathione aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN);
   * Glutamic aminotransferase (ALT) ≤ 3 times ULN;
   * Total bilirubin ≤ 1.5 times ULN, unless the patient has documented Gilbert syndrome. Patients with Gilbert-Meulengracht syndrome with total bilirubin ≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN may be included;
   * Serum creatinine ≤ 1.5 times ULN or a creatinine clearance ≥ 60 ml/min;
   * Hemoglobin ≥ 80 g/L or hemoglobin maintained at that level following transfusion;
   * International Normalized Ratio (INR) ≤ 1.5 times ULN and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times ULN;
   * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L.
   * A platelet count ≥ 50 x 10\^9/L or a platelet count maintained at that level following a platelet transfusion;
   * Left ventricular ejection fraction (LVEF) ≥ 45%.
9. Female patients with childbearing potential should have a negative pregnancy test during the screening period. Any male and female patients of childbearing potential must agree to use an effective contraception method for at least six months from the time that they sign the informed consent form until the end of the cell infusion. Female patients without childbearing potential (meeting at least 1 of the following criteria) is described below.

   * Have undergone a hysterectomy or bilateral oophorectomy;
   * Medically recognized as ovarian failure;
   * Medically recognized as post-menopausal (at least 12 consecutive months of menopause without pathological or physiological cause).

Exclusion Criteria:

1. Subject is confirmed to have morphological relapse of leukemia or positive MRD after allo-HSCT.
2. Subject with extramedullary infiltration of leukemia.
3. Suffer from other malignancies within 5 years prior to screening, except adequately treated carcinoma in situ of the cervix, basal cell or squamous epithelial cell skin cancer, post-radical thyroid cancer, and post-radical ductal carcinoma in situ.
4. Has severe respiratory disease (previous or combined history of severe interstitial lung disease, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm).
5. A previous history of a definite neurological or psychiatric disorder, including epilepsy or dementia.
6. Evidence of active central nervous system invasion or cranial neuropathy.
7. Patients with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titration assay not within the normal reference range, positive hepatitis C virus (HCV) antibody and peripheral blood HCV RNA ,positive for human immunodeficiency virus (HIV), or positive for cytomegalovirus (CMV) DNA, or positive syphilis test.
8. Subject who is allergic to the excipients of RC1012 injection or other drugs recommended in the study protocol (e.g., tolimumab, etc.).
9. Serious cardiac disease, including but not limited to severe arrhythmia, unstable angina, massive heart attack, New York Heart Association class III or IV cardiac insufficiency, refractory hypertension.
10. Persons who have previously received an organ transplant or are preparing to receive an organ transplant (except for HSCT).
11. Subject who has received other maintenance therapy drugs after HSCT or who wish to receive other maintenance therapy.
12. Subject with the presence of acute GvHD of degree III to IV or extensive chronic GvHD.
13. Active neurological autoimmune or inflammatory diseases (e.g. Guillain-Barre Syndrome (GBS), Amyotrophic lateral sclerosis (ALS)).
14. Clinically significant active cerebrovascular disease (e.g. cerebral oedema, Posterior Reversible Encephalopathy Syndrome (PRES)).
15. Subject with a life expectancy of less than 3 months.
16. Subject has been involved in other clinical studies within 3 months prior to screening.
17. Subject , in the judgement of the investigator and/or clinical criteria, is contraindicated to any study procedure or have other medical conditions that may place them at unacceptable risk.

Where this trial is running

Hefei, Anhui

• The First Hospital of the University of Science and Technology of China — Hefei, Anhui, China (Recruiting)

Study contacts

• Principal investigator: Xiaoyu Zhu, MD, PhD — Anhui Provincial Hospital
• Study coordinator: Xiaoyu Zhu, MD, PhD

Conditions Acute Myeloid Leukemia; allo-HSCT; Cell Therapy; AML; off-the-shelf cell product