CELL INTELLIGENCE · 肿瘤细胞治疗研究

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.

主要终点：Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0 · From recruitment to 24 weeks after the last treatment.
次要终点：Complete Response (CR) rate；Partial Response (PR) rate；Overall Response (OR) rate；Response time；Duration of Relief（DOR）

• MSC · EXPERIMENTAL · Mesenchymal stem cells: intravenous infusion, 2×10⁶ cells/kg body weight/week (once weekly), with 1 to 4 administrations based on different dosage groups.

This study is a single arm, open label, exploratory clinical study aimed at evaluating the efficacy, and safety of allogeneic umbilical cord blood-derived mesenchymal stem cells in the treatment of long-term cytopenia after CAR-T therapy.