Acute Myeloid LeukemiaPhase 1NCT05471323
Phase I Clinical Trial of RC1012 Injection in Patients With r/r AML
A Phase 1 study testing RC1012 injection (allo-DNT cells) in people with Acute Myeloid Leukemia, run by Guangdong Ruishun Biotech Co., Ltd at 1 site in China.
Trial summary
To evaluate the safety and tolerability of RC1012 infusion in patients with relapsed or refractory Acute Myelocytic Leukemia (r/r AML). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- RC1012 injection (allo-DNT cells)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 14 Jan 2021to 31 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 20Show fewer
- 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
- Left ventricular ejection fraction (LVEF) ≥ 45%.
- 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).
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
First Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, 310003
Huili Zhou, MD, PhD, 086-0571-87236685, 1482055406@qq.com
About this study
Official title: 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).
Read the detailed description
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.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- RC1012 injection (allo-DNT cells)
- Keywords
- r/r AML, Cell Therapy
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: RC1012 injection (allo-DNT cells) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 28 days
Maximum Tolerated Dose (MTD)
MTD was the highest dose for DLT in ≤1/6 subjects
Measured: Up to 28 days
Incidence of abnormalities
Incidence of abnormalities in AE/SAE/laboratory tests/electrocardiograms/vital signs.
Measured: Up to 28 days
Secondary outcomes (9)
Pharmacokinetics (PK) indicator (Cmax)
The peak concentration of allo-DNT cells amplified in the peripheral blood (Cmax, detected by Flow Cytometry).
Measured: Up to 90 days
Pharmacokinetics (PK) indicator (AUC)
Allo-DNT cells blood concentrations will be measured at different time points to evaluate the area under the curve (AUC). (AUC, detected by Flow Cytometry).
Measured: Up to 2 years
Pharmacokinetics (PK) indicator (Tmax)
Allo-DNT cells blood concentrations will be measured at different time points to evaluate the peak time (Tmax) in peripheral blood. Tmax is defined as the time to reach the highest concentration (Tmax, detected by Flow Cytometry).
Measured: Up to 2 years
Pharmacokinetics (PK) indicator (T1/2)
Allo-DNT cells blood concentrations will be measured at different time points to evaluate the elimination half-life in hours (T1/2). T1/2 is defined as the time point when the concentration of allo-DNT reaches half of maximum in a patient's peripheral blood (T1/2, detected by Flow Cytometry).
Measured: Up to 2 years
Overall Response Rate
ORR includes complete response (CR), CRi and PR. CR was defined as < 5% bone marrow blasts in an aspirate with spicules, no blasts with Auer rods or persistence of extramedullary disease, and independent of transfusions; CRi: was defined as<5% bone marrow blasts, either ANC<1×10^9/L or platelets<100×10^9/L, transfusion independence but with persistence of cytopenia; PR was defined as decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow aspirate and the normalization of blood counts.
Measured: Up to 2 years
Event-Free Survival
From the date of enrollment in the clinical trial until the failure of treatment, relapse or death.
Measured: Up to 2 years
Duration of Response
The time from the start of the first assessment of CR or PR to the first assessment as disease recurrence or progression or death
Measured: Up to 2 years
Relapse-Free Survival
Relapse-free survival is the time from study enrollment until documented disease relapse, or death from any cause.
Measured: Up to 2 years
Overall Survival
From the date of entry into the clinical study until death from any cause.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2022
- Study start14 Jan 2021
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Ruishun Biotech Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- First Affiliated Hospital of Zhejiang University
- Responsible party
- Sponsor
- Investigators
- Zhen Cai, MD, PhD, Principal investigator, First Affiliated Hospital of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05471323
- Sponsor's protocol ID
- RC1012-AML001
- Status last verified
- Aug 2022
- First submitted
- 20 Jul 2022
- Last updated
- 19 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05471323
- Acronym / sponsor ID
- RC1012-AML001
- Conditions
- Acute Myeloid Leukemia
- Keywords
- r/r AML, Cell Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Guangdong Ruishun Biotech Co., LtdIndustry (pharma, biotech, devices)
- Collaborators
- First Affiliated Hospital of Zhejiang University
- Study start
- 14 Jan 2021 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 22 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety and tolerability of RC1012 infusion in patients with relapsed or refractory Acute Myelocytic Leukemia (r/r AML).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RC1012 injection (allo-DNT Cells) | Experimental | Biological: RC1012 injection (allo-DNT cells)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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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).
- 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.
Key exclusion criteria (13 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RC1012 injection (allo-DNT cells)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. | Biological | RC1012 injection (allo-DNT Cells) |
Primary outcome
Dose-Limiting Toxicity (DLT)
Time frame: Up to 28 days
To evaluate the safety, tolerability, and determine the recommended dosage of allo-DNT Cell Therapy for Relapsed/Refractory Acute Myelocytic Leukemia
Maximum Tolerated Dose (MTD)
Time frame: Up to 28 days
MTD was the highest dose for DLT in ≤1/6 subjects
Incidence of abnormalities
Time frame: Up to 28 days
Incidence of abnormalities in AE/SAE/laboratory tests/electrocardiograms/vital signs.
9 secondary outcomes
Pharmacokinetics (PK) indicator (Cmax)
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (AUC)
Time frame: Up to 2 years
Pharmacokinetics (PK) indicator (Tmax)
Time frame: Up to 2 years
Pharmacokinetics (PK) indicator (T1/2)
Time frame: Up to 2 years
Overall Response Rate
Time frame: Up to 2 years
Event-Free Survival
Time frame: Up to 2 years
Duration of Response
Time frame: Up to 2 years
Relapse-Free Survival
Time frame: Up to 2 years
Overall Survival
Time frame: Up to 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2023.
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhen Cai, MD, PhD principal investigator
First Affiliated Hospital of Zhejiang University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RC1012 injection (allo-DNT cells) in people with Acute Myeloid Leukemia, run by Guangdong Ruishun Biotech Co., Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhen Cai, MD, PhD (+086-0571-56734707, caizhen1@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-Limiting Toxicity (DLT) (time frame: Up to 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2023.