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

NCT05471323 | Unknown Phase 1

• 1 other identifier: RC1012-AML001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Acute Myeloid Leukemia

Keywords

r/r AML; Cell Therapy

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 Relapsed/Refractory Acute Myelocytic Leukemia

  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 (9)

• Pharmacokinetics (PK) indicator (Cmax)

  Up to 90 days

• 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

• Overall Response Rate

  Up to 2 years

Study Arms (1)

RC1012 injection (allo-DNT Cells)

EXPERIMENTAL

Experimental: RC1012 injection (allo-DNT Cells) The trial is divided into two parts: Part A1 is a single- dose escalation trial with three dose groups (5×10\^7 cells/kg, 1.5×10\^8 cells/kg, 4.5×10\^8 cells/kg), with 9-18 patients planned to be enrolled. Part A2 is a multiple-dose escalation trial consisting of 2 dose groups (1.5×10\^8 cells/kg and 4.5×10\^8 cells/ kg at day 0, day 7 and day 14), with 9-12 patients planned to be enrolled. Part B is a multiple-dose extension trial in which the Safety Review Committee evaluates whether to extend an additional 3-6 patients to receive the multiple cell infusions based on available PK and safety data.

Biological: RC1012 injection (allo-DNT cells)

Interventions

RC1012 injection (allo-DNT cells) BIOLOGICAL

RC1012 injection (allo-DNT cells) 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.
• 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).
• 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).
• ECOG score 0 to 1.
• 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

You may not qualify if:

• A diagnosis of acute promyelocytic leukemia.
• Patients with extramedullary infiltration of leukemia.
• Evidence or history of 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.
• 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).
• 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 hematopoietic stem cell transplantation)
• Persons with acute and chronic graft-vs-host disease (GVHD)
• Those who have received a hematopoietic stem cell transplant within 2 months prior to screening tests.
• 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)).
• Patients with a life expectancy of less than 3 months
• Patients have been involved in other clinical studies within 3 months prior to screening.
• 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.

Sponsors & Collaborators

• Guangdong Ruishun Biotech Co., Ltd: lead
• First Affiliated Hospital of Zhejiang University: collaborator

Study Sites (1)

First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310003, 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

• Zhen Cai, MD, PhD

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhen Cai, MD, PhD

CONTACT

+086-0571-56734707; caizhen1@sina.com

Jingsong He, MD, PhD

CONTACT

086-13600547247; hejingsong@zju.edu.cn

Study Design

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

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: July 22, 2022
• Study Start: January 14, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: May 19, 2023

Record last verified: 2022-08

Locations

CN (1)