Umbilical cord mesenchymal stem cell treatment for persistent cytopenia after CAR‑T

Single-Arm, Exploratory Clinical Study to Evaluate the Safety and Efficacy of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in the Treatment of Long-Term Cytopenia After CAR-T Therapy

This trial will try giving umbilical cord blood–derived mesenchymal stem cells to adults with persistent severe low blood counts three weeks after CAR‑T therapy to see if their blood counts recover and to check safety.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy
• Locations: 1 site (Tianjin)
• Trial ID: NCT07212335 on ClinicalTrials.gov

What this trial studies

This is a single-center, open-label, dose‑escalation (3+3) trial testing allogeneic umbilical cord blood–derived mesenchymal stem cell infusions in adults with ALL, lymphoma, or myeloma who have severe cytopenia persisting three weeks after CAR‑T. All cohorts receive a standard cell dose of 2×10^6 cells/kg with groups differing by infusion frequency (one, two, or four infusions); 3 patients are enrolled per dose level with total enrollment planned between 15 and 24. Safety is monitored with a 28‑day DLT window and follow-up visits weekly for 8 weeks then monthly through 24 weeks; cell product release follows GMP and pathogen/purity/tumorigenicity testing. The primary focus is on preliminary safety and signals of hematologic recovery to inform dose selection for later studies.

Who should consider this trial

Good fit: Adults (≥18) with acute lymphoblastic leukemia, lymphoma, or multiple myeloma who still have severe neutropenia, thrombocytopenia, or anemia three weeks after CAR‑T infusion and meet performance and safety criteria are the intended candidates.

Not a fit: Patients with active uncontrolled infection, progressing marrow disease, poor performance status or limited life expectancy, or who do not meet safety or pregnancy/contraception requirements are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the treatment could speed recovery of blood counts and reduce infections, transfusions, and hospitalization after CAR‑T.

How similar studies have performed: Mesenchymal stem cells have shown mixed but promising early results for marrow support and immune complications in other settings, but use specifically for prolonged cytopenia after CAR‑T is novel and not yet well established.

Eligibility criteria

Inclusion Criteria

Patients must meet all the following criteria to be enrolled in this study:

* 1.Voluntarily participate in the study and sign the informed consent form;
* 2.Aged ≥ 18 years, regardless of gender;
* 3.Patients with acute lymphoblastic leukemia (ALL), lymphoma, or myeloma who still have severe cytopenia (meeting any of the following conditions: absolute neutrophil count ≤ 1×10⁹/L; platelet count ≤ 30×10⁹/L; hemoglobin ≤ 70 g/dL) 3 weeks after CAR-T cell infusion;
* 4.ECOG performance status score ≤ 2;
* 5.Estimated survival time ≥ 6 months;
* 6.For female patients of childbearing potential, a negative pregnancy test result is required. Female patients of childbearing potential and male patients must use highly effective contraceptive measures during the study period and for 4 months/6 months after the discontinuation of treatment, respectively.

Exclusion Criteria

Patients with any of the following conditions are prohibited from enrolling in this study:

* 1.Having received other anti-tumor treatments (including but not limited to chemotherapy, radiotherapy, targeted therapy, immunotherapy, or hematopoietic stem cell transplantation) that may affect the hematopoietic system or blood cell count within 1 month before the screening period after CAR-T cell infusion;
* 2.Significant bone marrow infiltration by tumor cells during the screening period (for ALL: bone marrow morphological examination showing leukemia cell proportion \> 5%; for multiple myeloma (MM) and lymphoma: bone marrow flow cytometry showing positive minimal residual disease (MRD), or bone marrow pathological immunohistochemistry showing lymphoma/clonal plasma cell infiltration);
* 3.Presence of any of the following conditions within 1 week before the first dose administration: infection with hemodynamic instability (requiring vasoactive drug support); deep fungal infection confirmed by imaging or microbiology (e.g., invasive aspergillosis, bloodstream infection, etc.); Pneumocystis jirovecii pneumonia, active tuberculosis, viremia (cytomegalovirus, parvovirus B19, etc.), and viral pneumonia (cytomegalovirus, COVID-19 virus, influenza virus, adenovirus, parainfluenza virus, etc.); as well as other severe infections that may affect hematopoiesis as judged by the investigator;
* 4.Serum creatinine or blood urea nitrogen ≥ 1.5 times the upper limit of normal (ULN);
* 5.Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times ULN; total bilirubin ≥ 1.5 times ULN;
* 6.Other severe and/or uncontrolled diseases, or conditions that may affect study participation as judged by the investigator, including but not limited to: severe cardiac rhythm or conduction abnormalities (e.g., ventricular arrhythmias requiring clinical intervention, second-degree to third-degree atrioventricular block, etc.), corrected QT interval using Fridericia's formula (QTcF) \> 480 ms on electrocardiogram; New York Heart Association (NYHA) heart function classification of Grade Ⅲ-Ⅳ; uncontrolled diabetes mellitus (glycated hemoglobin \[HbA1c\] \> 9%); refractory hypertension; chronic obstructive pulmonary disease (forced expiratory volume in 1 second \[FEV1\] \< 50% of predicted value), etc.;
* 7.History of arteriovenous thrombosis or atherosclerosis;
* 8.Positive for anti-human immunodeficiency virus (HIV) antibody or anti-Treponema pallidum specific antibody; positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core antibody with hepatitis B virus deoxyribonucleic acid (HBV-DNA) \> ULN; or hepatitis C virus ribonucleic acid (HCV-RNA) \> ULN;
* 9.A history of or current malignant solid tumor (except cured non-invasive basal cell or squamous cell carcinoma of the skin and/or other cured carcinoma in situ; except other malignant tumors that have achieved clinical cure for \> 5 years with no recurrence within 5 years);
* 10.Within 6 months after allogeneic hematopoietic stem cell transplantation, or donor cell chimerism rate ≤ 95%, or presence of active acute graft-versus-host disease (aGVHD) of Grade Ⅱ or higher, or moderate to severe chronic graft-versus-host disease (cGVHD);
* 11.Having received a live vaccine within 4 weeks before the first dose administration, or planning to receive any live vaccine during the study period;
* 12.Pregnant or lactating female patients;
* 13.Patients with mental disorders;
* 14.Participation in any other study drug trial (including vaccine trials) or exposure to other study drugs within 4 weeks or 5 half-lives (whichever is longer) before the first dose administration;
* 15.Patients who refuse to sign the informed consent form;
* 16.Other conditions deemed unsuitable for study inclusion by the investigator.

Where this trial is running

Tianjin

• Chinese Academy of Medical Sciences Hospital of Hematology (Chinese Academy of Medical Sciences Institute of Hematology) — Tianjin, China (Recruiting)

Study contacts

• Study coordinator: Zhenzhen Wang

Conditions Immune Effector Cell Associated Hematotoxicity; ICAHT; hematotoxicity; CAR-T; cytopenia