HY001N for Patients With Autoimmune Hemolytic Anemia After Failure ≥3 Lines of Therapy.

Official title

A Multi-center, Open-label, Single-arm Phase I Study to Assess the Safety, and Tolerability of HY001N Cell Injection in Patients With Autoimmune Hemolytic Anemia After Failure of Three or More Lines of Therapy

Overview

The goal of this clinical trial is to learn if HY001N cell injection safety and tolerability in adult patients with autoimmune hemolytic anemia after failure of 3 or more lines of therapy. It will also learn about the efficacy of HY001N cell injection to treat adult patients with autoimmune hemolytic anemia. The main questions it aims to answer are: Proportion of participants attaining a CR (defined as normalization of hemoglobin not attributed to transfusion effect and the normalization of hemolytic markers) or CRi (defined as normalization of hemoglobin not attributed to transfusion effect without normalization of hemolytic markers) after HY001N infusion? Proportion of participants attaining a PR (defined as hemoglobin ≥ 100 g/L or at least ≥ 20 g/L increase from baseline not attributed to transfusion effect) after HY001N infusion. • What medical problems do participants have when taking HY001N cell injection? Researchers will see if HY001N cell injection works to treat autoimmune hemolytic anemia. Participants will: * Take apheresis, lymphodepletion regimen and HY001N cell injection. * Visit the clinic on schedule.

Detailed description

This study will be conducted in Chinese hospitals and to include 9 to 12 subjects with refractory/relapsed autoimmune hemolytic anemia.

The main purpose of the study is to evaluate the safety and tolerability of HY001N Cell Injection in the treatment of autoimmune hemolytic anemia that has failed at least three lines of treatment, and determine the recommended phase II dose (RP2D) of HY001N Cell Injection in subjects with autoimmune hemolytic anemia who have failed at least three lines of treatment.

The Secondary purpose of the study is to evaluate the efficacy of HY001N Cell Injection in the treatment of autoimmune hemolytic anemia that has failed at least three lines of treatment and to evaluate the pharmacokinetic (PK) characteristics, pharmacodynamic (PD) characteristics and immunogenicity in the treated patients.

Interventions

• Drug HY001N Cell Injection
  Drug: HY001N Cell Injection The dose was incremented according to the "3+3" principle, and the three dose levels A, B and C were given in sequence at one time, which were respectively: A-1 dose group: 0.25×10\^5 CAR-T live cells /kg body weight Group A (initial dose) : 0.5×10\^5 CAR-T live cells /kg body weight Group B: 1.0×10\^5 CAR-T live cells /kg body weight Group C: 1.5×10\^5 CAR-T live cells /kg body weight

Primary outcome measures

• Incidence of Treatment-related Adverse Events [Time frame: Up to 28 days post-infusion]
• The safe dosage for a single infusion of HY001N Cell Injection [Time frame: Up to 28 days post-infusion]

Secondary outcome measures (3)

• Overall Remission Rate (ORR) [Time frame: Six months post-infusion]
• Changes in laboratory test indicators [Time frame: Up to 24 months post-infusion]
• Drug-free Remission (DFR) [Time frame: Up to 24 months post-infusion]

Eligibility criteria

Inclusion criteria

• Participant and/or participant's legal representative fully understand and voluntarily sign informed consent forms;
• Aged 18 to 75 years, regardless of gender;
• Participants with autoimmune hemolytic anemia or Evans syndrome after Failure ≥3 lines of therapy. The Failure of ≥3 lines of therapy meet all the following conditions: Hemoglobin less than 10g/dL and symptoms of anemia;

For participants diagnosed warm AIHA, or mixed AIHA, or Evans syndrome:

Failure of first-line corticosteroid therapy; Failure of second-line rituximab therapy; Failure of any one or more of the third-line treatments (splenectomy, cyclosporine, cyclophosphamide, azathioprine, mycophenolate mofetil, fludarabine, bortezomib, etc.)

For participants diagnosed cold AIHA (cold agglutinin disease):

Failure of first-line rituximab therapy; Failure of second-line rituximab ± Bendamostine/fludalabine; Failure of third-line therapy (bortezomib, Sutimlimab, Pegcetacoplan, Eculizumab, etc.)

• Women of childbearing age must have a negative blood pregnancy test within 7 days prior to the initiation of conditioning. Any male or female subject of reproductive potential must agree to use effective contraception throughout the study period and for at least 2 year following the infusion of CAR T-cells. In the judgment of the investigator, a subject of reproductive potential refers to having the biological capacity to conceive or father a living child and being sexually active. Women who considered infertile (i.e., meeting at least one of the following criteria): Has undergone a hysterectomy or bilateral oophorectomy, or Medically confirmed ovarian failure, or is medically confirmed as postmenopausal (defined as at least 12 consecutive months of amenorrhea without pathological or physiological causes).
• Laboratory tests of adequate organ function: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN; Coagulation profile: INR ≤ 1.5×ULN and aPTT ≤ 1.5×ULN; Serum creatinine ≤1.5×ULN or CCr ≥ 60mL/min; and have a minimum level of pulmonary reserve defined as the blood oxygen saturation in a non-oxygenated state is > 91%.
• Eastern Cooperative Oncology Group (ECOG) performance status 0\~2.

Exclusion criteria

• History of lymphoproliferative neoplasms
• Secondary AIHA caused by drugs or infection
• Pregnancy or lactation
• Previously received organ or hematopoietic stem cell transplantation
• History of new thrombotic event or organ infarction in the past 6 months
• Diagnosis of the active stage of connective tissue disease
• Had other inherited or acquired hemolytic diseases
• Have active infections, such as sepsis, bacteremia, fungemia, uncontrolled pulmonary infection and active tuberculosis, etc.
• Positive hepatitis B surface antigen (HBs-Ag) or hepatitis B e antigen (HBe-Ag); positive hepatitis B e antibody (HBe-Ab) or hepatitis B core antibody (HBc-Ab), and the HBV-DNA copy number is above the lower limit of the measurable capacity; positive hepatitis C (HCV) antibody; positive human immunodeficiency virus (HIV) antibody; positive syphilis test; EBV-DNA or CMV-DNA copy number is above the lower limit of the measurable capacity;
• Received major surgery within 4 weeks before screening that was assessed by the researcher as unsuitable for enrollment
• Have malignant tumors within 5 years before enrollment, except tumors with negligible risk of metastasis or death and curable tumors, such as adequately treated cervical carcinoma in situ, cutaneous basal cell carcinoma, etc.
• Have any of the following cardiovascular diseases: a. Left ventricular ejection fraction (LVEF) ≤45%, b. presence of active heart disease or congestive heart failure (New York Heart Association \[NYHA\] Class III or IV)), c. severe arrhythmias requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia), d. QTcB interval

≥450ms for male and ≥470ms for female, e. have myocardial infarction, bypass surgery, or stent placement within the 6 months before the trial, f. other heart diseases judged by the researcher to be unsuitable for enrollment

• Have a history of live attenuated vaccines within 6 weeks before enrollment
• Participate in other experimental studies within 30 days prior to apheresis or within 5 half-lives of the trial drug, whichever is longer. (Note: Parallel enrollment in studies is allowed)
• Have a history of epilepsy or other active central nervous system diseases
• Active bleeding
• Have an allergy to the ingredients of the medicine used in this trial
• Previously received CAR T-cell therapy
• Participants considered to be ineligible for the study by the investigator for reasons other than the above.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Institute of Hematology & Blood Diseases Hospital — Tianjin

Identifiers

NCT: NCT07748533 · HY001N101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗