CD180 CAR-T for relapsed or refractory CD180-positive blood cancers

CD180 CART Cell Injection in the Treatment of Relapsed or Refractory CD180 Positive Hematologic Malignancies: a Prospective, Single-arm, Single-center Clinical Study.

This trial will test whether an intravenous CD180 CAR‑T cell therapy can help adults with relapsed or refractory CD180‑positive AML or B‑ALL/LBL.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, CART, cyclophosphamide, Fludarabine
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07106749 on ClinicalTrials.gov

What this trial studies

This is a single-center, open‑label Phase I trial that enrolls two cohorts: relapsed/refractory acute myeloid leukemia (AML) and relapsed/refractory B‑cell acute lymphoblastic leukemia/lymphoma (B‑ALL/LBL). Participants must have CD180‑positive tumor cells and at least 5% bone marrow blasts, and each cohort will enroll about 6–12 patients. A 3+3 dose‑escalation with rapid titration will test three dose levels (0.5, 1, and 3 ×10^6 CAR‑T cells/kg) after fludarabine/cyclophosphamide lymphodepletion. The primary focus is safety and identifying a tolerated dose, with secondary observations of anti‑tumor activity.

Who should consider this trial

Good fit: Adults aged 18–69 with relapsed or refractory CD180‑positive AML or B‑ALL/LBL and ≥5% bone marrow blasts who can tolerate lymphodepleting chemotherapy are the intended candidates.

Not a fit: Patients whose tumors do not express CD180, who are not relapsed/refractory, who have very low blast counts, or who cannot undergo preconditioning chemotherapy are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, CD180 CAR‑T could induce remissions in patients with CD180‑positive disease who have exhausted standard therapies.

How similar studies have performed: CAR‑T therapies targeting other B‑cell antigens (for example CD19) have produced remissions in B‑cell malignancies, but CD180‑directed CAR‑T is a relatively novel approach with limited clinical experience.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 and \<70 years, regardless of gender;
2. B-ALL/LBL was diagnosed according to the criteria of NCCN Clinical Practice Guidelines for Acute Lymphocytic Leukemia (2020.v1) and B-cell Lymphoma Clinical Practice Guidelines (2020.v1);
3. Patients diagnosed with AML with reference to the Guidelines for Diagnosis and Treatment of Adult Acute Myeloid Leukemia (2018 Edition) issued by the Health Commission;
4. Cytology confirmed that the tumor cells were CD180 positive.
5. Number of blasts in bone marrow ≥5% at screening (bone marrow morphology);
6. Complies with the diagnosis of relapsed/refractory AML, including any of the following conditions according to China Guidelines for Diagnosis and Treatment of Relapsed/Refractory Acute Myeloid Leukemia (2021 Edition):

   1. Primary refractory patients who did not achieve CR after two cycles of standard induction chemotherapy;
   2. CR after consolidation chemotherapy, relapse within 12 months;
   3. Relapse 12 months after remission but ineffective after conventional chemotherapy;
   4. 2 or more relapses;
   5. Relapse after hematopoietic stem cell transplantation.
7. Meet the diagnosis of relapsed/refractory B-ALL/LBL, including any of the following:

   1. Primary refractory patients who have not achieved complete response after two cycles of standard chemotherapy, or patients who have not achieved complete response after multi-line rescue chemotherapy;
   2. Relapse within \<12 months after complete remission or ≥12 months after complete remission and fail to achieve complete remission induced by 1 or more cycles of standard treatment;
   3. Relapse after hematopoietic stem cell transplantation or relapse after CAR-T therapy at the same target;
8. Complies with diagnosis of other relapsed/refractory CD180 positive hematologic malignancies
9. Creatine clearance \>60ml/min (Cockcroft and Gault formula); serum total bilirubin ≤3 times the upper limit of normal, serum ALT and AST ≤5 times the upper limit of normal range for patients without liver invasion;
10. Echocardiography showing left ventricular ejection fraction (LVEF) ≥50%;
11. Pulse oxygen saturation ≥92%;
12. The estimated survival time is more than 3 months;
13. ECOG score 0-2;
14. Subjects or their legal guardians voluntarily participate in this trial and sign the informed consent form.

Exclusion Criteria:

Subjects who met any of the following criteria were excluded from the study:

1. acute promyelocytic leukemia (APL);
2. Presence of a genetic syndrome such as Fanconi's anemia, Kostmann's syndrome, Shwachman syndrome or any other known syndrome of bone marrow failure;
3. Patients with uncontrolled active central nervous system leukemia (CNSL), i.e. cerebrospinal fluid grades CNS 2 and CNS 3;
4. Patients who have received anti-tumor therapy before infusion should be excluded if any of the following conditions are met:

   1. Systemic chemotherapy (except for pretreatment) within 1 week;
   2. For those who have received monoclonal antibody therapy, the last time of monoclonal antibody infusion is less than 5 half-lives or 4 weeks (whichever is shorter) at screening;
   3. Received donor lymphocyte infusion (DLI) within 6 weeks;
5. Presence of uncontrolled, serious, active infection at screening;
6. Patients with a history of serious heart disease, including: severe cardiac insufficiency (subjects with cardiac insufficiency of Class III or IV according to the New York Heart Association (NYHA) cardiac function classification standard), myocardial infarction within 12 months or cardiac angioplasty or stenting, unstable angina pectoris, ECG indicating significant QT interval prolongation (\>480ms) or serious arrhythmia judged by the investigator;
7. Previous craniocerebral trauma, disturbance of consciousness, epilepsy, cerebral ischemia, cerebral vascular hemorrhagic disease and other medical history, and within six months of the need for drug treatment;
8. Patients with hepatitis B surface antigen (HBsAg) greater than 10E6 IU/mL, hepatitis C virus (HCV) antibody positive, human immunodeficiency virus (HIV) antibody positive, syphilis antibody test positive, EBER positive or EBV copy number greater than the upper limit of normal at screening;
9. Patients who must use steroid hormones during CAR-T infusion (except for local or inhaled steroid hormones); subjects who are receiving systemic steroid therapy before screening and need long-term systemic steroid therapy during treatment according to the investigator's judgment (except for inhaled or local use);
10. Subjects with autoimmune diseases requiring treatment, immunodeficient subjects, or subjects requiring immunosuppressive treatment;
11. Patients with acute graft-versus-host disease (GvHD) or moderate-to-severe chronic GvHD within 4 weeks prior to screening;
12. Patients with a history of allergy to any component of cell products;
13. Pregnant, lactating females, and subjects (male or female) of childbearing potential who are unable to use effective contraception within 1 year after cell infusion; male subjects who plan to become pregnant within 1 year after cell infusion; female subjects or partners who plan to become pregnant within 1 year after cell infusion;
14. Any condition that, in the opinion of the investigator, may increase the risk to the subject or interfere with the results of the trial.

Where this trial is running

Tianjin, Tianjin Municipality

• Institute of Hematology & Blood Diseases Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: Jianxiang Wang

Conditions Acute Myeloid Leukemia; B Acute Lymphoblastic Leukemia/Lymphoma; CD180 CAR-T; Acute myeloid leukemia; B acute lymphoblastic leukemia/lymphoma; Prospective study; Single-arm Clinical Study