Hema-NeoTIL01 Cell Infusion Therapy in Relapsed/Refractory Acute Leukemia

Assessment of the Safety and Efficacy of Hema-NeoTIL01 Cell Infusion Therapy in Relapsed/Refractory Acute Leukemia: A Single-Arm, Open-Label, Prospective Study

This clinical trial aims to investigate the safety, optimal dosage, and effectiveness of autologous tumor-specific T cells, known as Hema-NeoTIL0 in treating relapsed/refractory B-ALL/AML.

Study Overview

• Status: Not yet recruiting
• Conditions: Leukemia, Myeloid, Acute; B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Biological: Hema-NeoTIL01

Detailed Description

Primary Objective:

To assess the safety of Hema-NeoTIL01 in the treatment of relapsed/refractory acute leukemia (B-ALL/AML).

Secondary Objective:

To evaluate the efficacy of Hema-NeoTIL01 in relapsed/refractory acute leukemia (B-ALL/AML).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Xiaowen Tang, Ph.D; Phone Number: (0086)51267780086; Email: xwtang1020@163.com
• Study Contact Backup: Name: Depei Wu, Ph.D; Phone Number: (0086)51267780086

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • the First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 and <70 years old, gender not specified;
2. Diagnosed with B-ALL or AML according to the World Health Organization (WHO) classification of hematopoietic and lymphoid tissue tumors (2022 version);
3. Meet the diagnosis of relapsed/refractory leukemia, excluding isolated extramedullary relapse; For relapsed or refractory ALL, including any of the following situations: a) Relapse: Peripheral blood or bone marrow recurrence of primitive cells >5% or extramedullary lesions appear again after complete remission; b) Refractory: Primary refractory patients who fail to achieve complete remission after standard induction chemotherapy; Or meet the diagnosis of relapsed or refractory AML, including any of the following situations: a) Relapse: Recurrence of primitive cells >5% in bone marrow after complete remission (except for reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary infiltration of leukemia cells; b) Refractory: Patients who have failed two cycles of standard treatment; those who relapse within 12 months after CR after consolidation therapy; those who relapse after 12 months and are ineffective after conventional chemotherapy; those with two or more relapses; those with persistent extramedullary leukemia;
4. Patients who have previously received ineffective/relapsed CAR-T cell therapy may be included in this study, provided that the efficacy evaluation of CAR-T therapy has been completed and evaluated as NR, or relapse after remission of CAR-T therapy;
5. Estimated survival >12 weeks;
6. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2;
7. Left ventricular ejection fraction (LVEF) ≥50%;
8. Pulmonary function ≤Grade 1 dyspnea (CTCAE v5.0), normal oxygen saturation without oxygen supplementation;
9. Total bilirubin (TBil) ≤3×upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5×ULN, creatinine ≤1.6mg/dL;
10. Pregnancy test must be negative, and fertile non-abstinent female patients must agree to use effective contraception from the start of self-screening to 1 year after cell infusion. Fertile male patients with fertile partners must agree to use effective contraception from the start of self-screening to 1 year after cell infusion, and should not donate semen or sperm throughout the study period.
11. The subject and their legal guardian voluntarily participate in this study, understand the trial information and objectives, and provide informed consent with a signed and dated signature.
12. The subject and their legal guardian are willing and able to comply with all trial requirements.

Exclusion Criteria:

1. Patients with a history of severe central nervous system diseases, such as uncontrolled seizures, stroke, severe brain injury resulting in aphasia, paralysis, dementia, Parkinson's disease, psychiatric disorders, etc.;
2. New York Heart Association (NYHA) functional class III or IV heart failure;
3. Any unstable diseases occurring within 6 months before screening (including but not limited to): unstable angina, ischemic or cerebrovascular accidents, myocardial infarction, severe arrhythmias requiring drug treatment (such as rapid atrial fibrillation, high-degree atrioventricular block, ventricular tachycardia, ventricular fibrillation, or torsades de pointes), cardiac catheterization or coronary artery stenting, or coronary artery bypass surgery, thrombotic or embolic events.
4. Presence of disseminated intravascular coagulation;
5. Severe autoimmune diseases or immunodeficiency diseases;
6. Active graft-versus-host disease requiring continued systemic therapy;
7. Subjects receiving systemic corticosteroids or other immunosuppressive therapy before screening, and the investigator determines that they will continue to use long-term therapy after enrollment (excluding inhalation or local use);
8. History of or concomitant active malignant tumors, excluding cured non-invasive basal cell or squamous cell skin cancer, uterine cervical carcinoma in situ or localized prostate cancer or breast ductal carcinoma in situ without recurrence for at least 2 years;
9. Presence of other severe medical conditions as determined by the investigator, such as uncontrolled hypertension or diabetes, severe renal insufficiency, severe pulmonary dysfunction, etc.;
10. Active HBV or HCV infection (HBV-DNA positive or HCV-RNA positive), HIV positive, or syphilis positive;
11. Other severe or persistent active infections;
12. Severity of adverse events related to previous systemic immunotherapy (including other investigational drugs or medical device interventions) at screening not reduced to grade 1 or baseline status;
13. Discontinuation of immunosuppressants within 2 weeks prior to screening;
14. History of allergy to any component of the cell product;
15. Vaccination or any surgical procedure within 4 weeks prior to screening;
16. Other conditions deemed by the investigator to potentially increase subject risk or interfere with trial results.

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: Hema-NeoTIL01 treatment; In this study, we adopted a 3+3 design with dose escalation. Initially, three dose groups were established: 2.0×10^7, 6.0×10^7, and 2.0×10^8 cells/kg. Each dose group received treatment on Days 0, 3, and 6 through i.v. injection, with bone marrow examination performed on Day 7 to assess tumor burden. Upon assessment by the investigators and discussion with the Safety Review Committee (SRC), it will be determined that whether patients may benefit from additional infusions. With SRC approval, the number of administrations could be increased, not exceeding a maximum of six doses. At the end of dose escalation, the SRC may decide to adjust the number of participants in the designated dose group as deemed appropriate.

Biological: Hema-NeoTIL01; Patients will receive intravenous infusion of Hema-NeoTIL01, which is a highly specific tumor infiltrating lymphocyte (TIL) product derived from patients' bone marrow or peripheral blood, expanded ex vivo through antigen presentation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR/CRi, MRD-negative CR	Complete remission (CR) is defined as the presence of less than 5% bone marrow blasts in an aspirate containing spicules, accompanied by independence from transfusions. CR with incomplete hematologic recovery (CRi) is defined as the presence of less than 5% bone marrow blasts, with either an absolute neutrophil count (ANC) of less than 1×10^9/L or a platelet count of less than 100×10^9/L, while remaining transfusion-independent but exhibiting persistent cytopenia. Minimal residual disease (MRD)-negative CR is defined as a leukemic cell count below the sensitivity threshold of 1×10^-4 (0.01%) of bone marrow mononuclear cells (MNCs), as measured by multiparameter flow cytometry.	Within 28 days after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RFS	Relapse-free survival (RFS) is defined as the interval from the date of achieving CR to the first occurrence of leukemia relapse, death, or the date of the last follow-up.	2 years
OS	Overall survival (OS) is defined as the duration from the time of enrollment to death from any cause.	2 years
Adverse events	The number of adverse events are evaluated with CTCAE V5.0.	Within 28 days after the first dose

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Study Chair: Xiaowen Tang, the First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: August 14, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: AML; B-ALL; T cell therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: Hema-NeoTIL01-SU01

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