Phase I Clinical Trial of RC1012 Injection in Patients With r/r AML

A Single-arm, Single/Multiple Dose-escalation and Dose-extension Phase I Clinical Trial of RC1012 Injection (Allogeneic DNT Cells) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

To evaluate the safety and tolerability of RC1012 infusion in patients with relapsed or refractory Acute Myelocytic Leukemia (r/r AML).

This study aims to evaluate the safety and tolerability of RC1012 injection in patients with relapsed or refractory Acute Myelocytic Leukemia (r/r AML).

DNT cells are mature T lymphocytes that comprise 3-10% of T cells in human peripheral blood mononuclear cells (PBMC). Allo-DNT cells from healthy donors have been proved to be safe and demonstrated potent cytotoxicity against AML blasts from AML patients in preclinical and preliminary clinical studies. Allo-DNT cells will be collected from healthy donors (NO MHC match needed) and infused into patients. The drug for this study is an off-the-shelf product. Patients DO NOT need to wait for the cell manufacturing.

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. Accordance with the diagnostic criteria of AML in the 2016 WHO staging and meeting the diagnostic criteria of relapsed and refractory in the Chinese Guidelines for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia (2017 edition).

   • Diagnostic criteria for Relapsed AML: reappearance of leukemic cells in peripheral blood or >5% primitive/naive cells in bone marrow after CR (except for other causes such as bone marrow regeneration after consolidation chemotherapy) or extra-marrow infiltration of leukemic cells.
   • Diagnostic criteria for refractory AML: primary refractory disease that has not achieved complete remission after two courses of induction chemotherapy with a standard regimen (containing cytarabine and an anthracycline or anthraquinone).

4. The patient has recovered from the toxicity of the prior treatment, i.e., less than a grade 2 CTCAE toxicity rating (unless the abnormality is tumor-related).

5. ECOG score 0 to 1.

6. Appropriate organ function, and accordance with the following criteria within 7 days prior to lymphodepleting chemotherapy.

   • 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 ≥ 60 g/L or hemoglobin maintained at that level following transfusion.
   • Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L.
   • A platelet count ≥ 30 x 10^9/L or a platelet count maintained at that level following a platelet transfusion
   • Left ventricular ejection fraction (LVEF) ≥ 45%.

7. Female patients with of 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. A diagnosis of acute promyelocytic leukemia.
2. Patients with extramedullary infiltration of leukemia.
3. Evidence or history of central nervous system invasion or cranial neuropathy.
4. 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.
5. Persons with hypersensitivity to excipients of RC1012 injection (e.g., human albumin) or other drugs recommended in the study protocol (e.g., lymphodepleting treatment, Tocilizumab).
6. 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.
7. Persons who have previously received an organ transplant or are preparing to receive an organ transplant (except for hematopoietic stem cell transplantation)
8. Persons with acute and chronic graft-vs-host disease (GVHD)
9. Those who have received a hematopoietic stem cell transplant within 2 months prior to screening tests.
10. Active neurological autoimmune or inflammatory diseases (e.g. Guillain-Barre Syndrome (GBS), Amyotrophic lateral sclerosis (ALS)) and clinically significant active cerebrovascular disease (e.g. cerebral oedema, Posterior Reversible Encephalopathy Syndrome (PRES)).
11. Patients with a life expectancy of less than 3 months
12. Patients have been involved in other clinical studies within 3 months prior to screening.
13. Patients, in the judgement of the investigator and/or clinical criteria, are contraindicated to any study procedure or have other medical conditions that may place them at unacceptable risk.