RC1012 Injection (Allo-DNT Cells) for the Prevention of Relapse in AML Patients After Allo-HSCT

NCT05858814 | Recruiting Phase 1

• 1 other identifier: RC1012-AML002
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of RC1012 injection infusion in AML Patients after Allo-HSCT

Conditions

Acute Myeloid Leukemia

Keywords

allo-HSCT; Cell Therapy; AML; off-the-shelf cell product

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT)

  To evaluate the safety, tolerability, and determine the recommended dosage of allo-DNT Cell Therapy for AML subjects after Allo-HSCT

  Up to 28 days

• Maximum Tolerated Dose (MTD)

  MTD was the highest dose for DLT in ≤1/6 subjects

  Up to 28 days

• Incidence of abnormalities

  Incidence of abnormalities in AE/SAE/laboratory tests/electrocardiograms/vital signs.

  Up to 28 days

Secondary Outcomes (8)

• Pharmacokinetics (PK) indicator (Cmax)

  Up to 2 years

• Pharmacokinetics (PK) indicator (AUC)

  Up to 2 years

• Pharmacokinetics (PK) indicator (Tmax)

  Up to 2 years

• Pharmacokinetics (PK) indicator (T1/2)

  Up to 2 years

• Recurrence rate at 6 months

  Up to 6 months

Study Arms (1)

RC1012 injection (allo-DNT Cells)

EXPERIMENTAL

The trial is divided into two parts: Part A is a dose escalation trial with two dose groups (1.0×10\^8 cells/kg, 1.5×10\^8 cells/kg at day 0, day 28 and day 56), with 6-12 patients planned to be enrolled. Part B is a dose-expansion randomized controlled trial in which 40-60 patients will receive RC1012 infusions at RP2D dose levels.

Biological: RC1012 injection (allo-DNT cells)

Interventions

RC1012 injection (allo-DNT cells) BIOLOGICAL

RC1012 injection (allo-DNT cells) are from healthy donors and 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 injected into patients. The drug for this study is an off-the-shelf product. Patients DO NOT need to wait for the cell manufacturing.

RC1012 injection (allo-DNT Cells)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign an ICF and expect to complete the study procedures for follow-up examinations and treatment.
• Aged 18 to 70 years (including cut-offs), regardless of gender.
• Subject must be diagnosed with AML according to World Health Organization (WHO) criteria (2016).
• 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.
• 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).
• The subject has recovered from the toxicity of the prior treatment, i.e., CTCAE toxicity grade \<2 (unless the abnormality is tumor-related).
• ECOG score 0 to 1.
• 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.

You may not qualify if:

• Subject is confirmed to have morphological relapse of leukemia or positive MRD after allo-HSCT.
• Subject with extramedullary infiltration of leukemia.
• 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.
• Has severe respiratory disease (previous or combined history of severe interstitial lung disease, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm).
• A previous history of a definite neurological or psychiatric disorder, including epilepsy or dementia.
• Evidence of active central nervous system invasion or cranial neuropathy.
• 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.
• Subject who is allergic to the excipients of RC1012 injection or other drugs recommended in the study protocol (e.g., tolimumab, etc.).
• 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.
• Persons who have previously received an organ transplant or are preparing to receive an organ transplant (except for HSCT).
• Subject who has received other maintenance therapy drugs after HSCT or who wish to receive other maintenance therapy.
• Subject with the presence of acute GvHD of degree III to IV or extensive chronic GvHD.
• Active neurological autoimmune or inflammatory diseases (e.g. Guillain-Barre Syndrome (GBS), Amyotrophic lateral sclerosis (ALS)).
• Clinically significant active cerebrovascular disease (e.g. cerebral oedema, Posterior Reversible Encephalopathy Syndrome (PRES)).
• Subject with a life expectancy of less than 3 months.

Sponsors & Collaborators

• Guangdong Ruishun Biotech Co., Ltd: lead
• Anhui Provincial Hospital: collaborator

Study Sites (1)

The First Hospital of the University of Science and Technology of China

Hefei, Anhui, 230001, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Xiaoyu Zhu, MD, PhD

  Anhui Provincial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaoyu Zhu, MD, PhD

CONTACT

086-15255456091; bayinhexy@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2023
• First Posted: May 15, 2023
• Study Start: May 4, 2023
• Primary Completion: May 27, 2024
• Study Completion (Estimated): June 24, 2026
• Last Updated: May 19, 2023

Record last verified: 2023-01

Locations

CN (1)