A Clinical Study to Explore the Safety and Efficacy of CT0991 in Relapsed/Refractory Acute Myeloid Leukemia (CT0991)

A Clinical Study to Investigate the Safety and Efficacy of CT0991 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

A Clinical Study to Investigate the Safety and Efficacy of CT0991 in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Study Overview

• Status: Suspended
• Conditions: Relapsed/Refractory Acute Myeloid Leukemia(AML)
• Intervention / Treatment: Drug: CAR-T cells（ chimeric antigen receptor T cells）

Detailed Description

This is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety, efficacy, and cellular pharmacokinetics of CT0991 in patients with relapsed or refractory acute myeloid leukemia. It is planned to enroll 9-24 participants in this trial.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The first affiliated hospital of medical college of zhejiang university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Volunteer to participate in the clinical trial; Fully understand and are informed of this study and sign the informed consent form; Willing to follow and able to complete all trial procedures；
2. Age 18-75 years (inclusive), male or female；
3. Estimated survival > 12 weeks;
4. Patients with relapsed or refractory AML as defined in the Chinese Guidelines for the Diagnosis and Treatment of Relapsed and Refractory Acute Myeloid Leukemia (Version 2023);
5. ECOG score 0-2;
6. Participants should meet the following test results (no ongoing ongoing supportive care): a)Left ventricular ejection fraction (LVEF) > 50%; b)ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, total bilirubin ≤ 2 × ULN; c)Endogenous creatinine clearance ≥ 30 mL/min (creatinine clearance calculated using the Cockcroft-Gault formula); d) Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN and prothrombin time (PT) ≤ 1.5 × ULN.
7. Female participants of childbearing potential must have a negative serum pregnancy test at screening and before receiving cleansing, be willing to use a highly effective and reliable method of contraception for 1 year after receiving trial treatment, and be absolutely prohibited from donating eggs for 1 year after receiving trial treatment during the trial;
8. Male participants willing to use a highly effective and reliable method of contraception for 1 year following trial treatment if sexually active with a woman of childbearing potential. All male participants were absolutely prohibited from donating sperm for 1 year after receiving trial treatment during the trial.

Exclusion Criteria:

1. The participant has any serious illness, laboratory abnormality, or psychiatric disorder that may impair the ability to receive or tolerate planned trial treatment; or the investigator judges that the participant 's participation in the clinical trial is not in his/her best interest (e.g., compromised health), or may hinder, limit, or confound protocol-specific assessments;
2. Participants were diagnosed with acute promyelocytic leukemia (APL), BCR-ABL positive leukemia (chronic myeloid leukemia in acute phase), secondary AML (other than MDS), central nervous system leukemia;
3. Participants with a history of epilepsy or other central nervous system disease;
4. Participants who have received autologous stem cell transplantation within 12 weeks or allogeneic stem cell transplantation within 6 months prior to screening;
5. Participant has clinically significant active GVHD or is receiving systemic corticosteroids for GVHD;
6. Participant has a second primary malignancy other than AML that has required treatment or has not been in complete remission within the past 2 years. The following cancers were considered curable, including nonmetastatic basal cell or squamous cell skin cancer, nonmetastatic prostate cancer, breast or cervical carcinoma in situ, and nonmuscle-invasive bladder cancer. Participants receiving ongoing hormonal therapy may be included in this trial at the discretion of the medical monitor in consultation with the investigator;
7. Participants had positive serology for human immunodeficiency virus (HIV) and syphilis, active hepatitis C virus (HCV) infection, or active hepatitis B virus (HBV) infection. Participants with a history of previously treated hepatitis B or C were allowed to be included in this trial if viral load could not be detected by qPCR and/or nucleic acid testing;
8. Major surgery within 14 days prior to washout or planned major surgery within 28 days after receiving CT0991 infusion. If required, the medical monitor and investigator must discuss to confirm whether the surgery is considered a major surgery before the participant is included in this trial;
9. Received anti-tumor therapy 14 days before Preconditioning, including chemotherapy, molecular targeted therapy;
10. Systemic therapeutic doses of glucocorticoids (defined as ≥ 20 mg prednisone or other equivalent per day) within 14 days prior to cleansing; however topical glucocorticoids such as topical dermal, eye drops, nasal sprays, inhalations, and physiologic replacement therapy doses of glucocorticoids are permitted ;
11. Vaccination with live attenuated vaccine or mRNA vaccine within 4 weeks prior to clear shower;
12. Allergic or intolerant to clear shower drugs and tocilizumab, or allergic to DMSO in cell infusion preparations, or previous history of other serious allergies such as anaphylactic shock;
13. Toxicities caused by previous treatment did not recover to Common Terminology Criteria for Adverse Events (CTCAE) ≤ Grade 1, except alopecia, peripheral neuropathy, and other events that were judged by the investigator to be unlikely to be cumulative toxicities due to clear shower or CT0991 infusion;
14. Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-T cells（ chimeric antigen receptor T cells）	Drug: CAR-T cells（ chimeric antigen receptor T cells）; CAR-T cells（ chimeric antigen receptor T cells）

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AE) after CT0991infusion	An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria	12 months after CT0991 infusion
Dose-limiting toxicity （DLT）	The DLT is evaluated as the proportion of patients who experienced adverse events related to CT0991 that meet the criteria for DLT events after the first infusion.	Up to 28 days after CAR-T cells infusion
MTD and/or dose range	Evaluate Dose limited toxicity and recommended dosage range after CT0991 infusion	Up to 28 days after CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (CR), and complete response with incomplete hematologic recovery (CRi)	Performed according to the Technical Guidelines for Clinical Development of New Drugs for Acute Myeloid Leukemia and ELN 2022 Criteria for AML defined of Achieve CR and CRi.	12 months after CT0991 infusion
complete response with partial hematologic recovery (CRh), Morphologic leukemia-free status (MLFS) and partial response (PR)	Performed according to the Technical Guidelines for Clinical Development of New Drugs for Acute Myeloid Leukemia and ELN 2022 Criteria for AML defined of Achieve CRh, MLFS and PR.	12 months after CT0991 infusion
Duration of response (DOR)	Participants achieving CR/CRi/CRh will be included in the analysis set for DOR. DOR is defined as the time from the date of confirmed response until the date of disease relapse or death from any cause, whichever occurs first.	12 months after CT0991 infusion
Event-free survival (EFS)	defined as the time from the date of receiving the infusion to the date of treatment failure (failure to achieve CR/CRh/CRi/MLFS/PR after both efficacy assessments), or relapse (hematologic relapse or extramedullary relapse after CR/CRh/CRi), or death from any cause, whichever occurs first. When an EFS event was "Ineffective Therapy", the primary analysis of EFS was performed on a 1-day basis (ie, time to treatment received as the event). For a more comprehensive assessment, sensitivity analyses could be performed using the actual date of treatment failure, end of treatment, or start of next-line anti-leukemia therapy as the end of EFS for treatment failure, respectively.	12 months after CT0991 infusion
Overall survival (OS)	defined as the time from the date of receiving the infusion to the date of death from any cause.	12 months after CT0991 infusion
Minimal Residual Disease (MRD) Negative Rate	tested in all participants who achieved CR/CRh/CRi. MRD negativity was defined as abnormal cells detected by the MFC method accounting for < 0.1% of CD45-positive cells (at least 500,000 CD45-positive cells detected).	12 months after CT0991 infusion
Test Copy number of CAR	Evaluate cellular pharmacokinetics of CT0991	12 months after CT0991 infusion

Collaborators and Investigators

• Sponsor: He Huang

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2025
• Primary Completion (Actual): August 17, 2025
• Study Completion (Estimated): August 17, 2026

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): November 29, 2024

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute
• Other Study ID Numbers: TXB2024024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No