Ignite Creation Date:
2025-12-24 @ 10:42 PM
Ignite Modification Date:
2025-12-25 @ 8:13 PM
Study NCT ID:
NCT07212335
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-10-08
First Post:
2025-09-30
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Safety and Efficacy of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in the Treatment of Long-Term Cytopenia After CAR-T Therapy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000095542', 'term': 'Cytopenia'}], 'ancestors': [{'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 15}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-10-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2027-10-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-30', 'studyFirstSubmitDate': '2025-09-30', 'studyFirstSubmitQcDate': '2025-09-30', 'lastUpdatePostDateStruct': {'date': '2025-10-08', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-10-08', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2026-10-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0', 'timeFrame': 'From recruitment to 24 weeks after the last treatment.'}], 'secondaryOutcomes': [{'measure': 'Complete Response (CR) rate', 'timeFrame': 'At Week 4 and Week 8 after the completion of MSC infusion', 'description': 'Complete Response (CR) Criteria (no red blood cell/platelet transfusion for at least 7 days and meeting the standard in two consecutive tests):\n\nHemoglobin (Hb) ≥ 100 g/L (for adults) or ≥ the lower limit of age-adjusted normal value; Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L; Platelet Count (PLT) ≥ 100×10⁹/L.'}, {'measure': 'Partial Response (PR) rate', 'timeFrame': 'At Week 4 and Week 8 after the completion of MSC infusion', 'description': 'Partial Response (PR) Criteria: Meeting any of the following conditions (no red blood cell/platelet transfusion for at least 7 days and meeting the standard in two consecutive tests):\n\nNeutrophils: Absolute value increased by ≥ 0.5×10⁹/L compared with the baseline; Platelets: Absolute value increased by ≥ 10×10⁹/L compared with the baseline; Hemoglobin: Absolute value increased by ≥ 15 g/L compared with the baseline.'}, {'measure': 'Overall Response (OR) rate', 'timeFrame': 'At Week 4 and Week 8 after the completion of MSC infusion', 'description': 'OR=PR+CR'}, {'measure': 'Response time', 'timeFrame': 'From the first MSC infusion to 8th week after the last MSC infusion', 'description': 'The median time from the first MSC infusion to the first achievement of CR/PR for various blood cell types.'}, {'measure': 'Duration of Relief（DOR）', 'timeFrame': 'from the date of achiving CR/PR to the earliest occurrence of hematopoietic indices falling below the CR/PR criteria or the end of the preset 24-week follow-up period after the first MSC infusion.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['ICAHT', 'hematotoxicity', 'CAR-T', 'cytopenia'], 'conditions': ['Immune Effector Cell Associated Hematotoxicity']}, 'descriptionModule': {'briefSummary': 'Primary Objective:\n\nTo observe and evaluate the safety and tolerability of umbilical cord blood-derived mesenchymal stem cells in the treatment of long-term cytopenia after CAR-T therapy.\n\nSecondary Objectives:\n\nTo preliminarily evaluate the efficacy of umbilical cord blood-derived mesenchymal stem cells in the clinical treatment of patients with long-term cytopenia after CAR-T therapy.\n\nTo explore the changes in immune indicators before and after the infusion of umbilical cord blood-derived mesenchymal stem cells.\n\nInvestigational Product:\n\nUmbilical cord blood-derived mesenchymal stem cell injection (MSC, UCell Life Science Development Co., Ltd.). The main component is human umbilical cord blood-derived mesenchymal stem cells cultured in vitro. Each bag contains 100 ml and 1.0 × 10⁸ mesenchymal stem cells.\n\nStudy Population Patients with acute lymphoblastic leukemia, lymphoma, and multiple myeloma who still have severe cytopenia 3 weeks after CAR-T reinfusion (meeting any of the following conditions: neutrophil count ≤ 1 × 10⁹/L; platelet count ≤ 30 × 10⁹/L; hemoglobin ≤ 70 g/dL).\n\nSample Size It is planned to enroll 15 - 24 patients. Study Design This is a single-center, exploratory clinical study initiated by investigators, aiming to evaluate the efficacy and safety of umbilical cord blood-derived mesenchymal stem cells in the treatment of long-term cytopenia after CAR-T therapy. The study is divided into two phases: dose escalation phase and dose expansion phase.\n\nIn the dose escalation phase, a "3 + 3" dose escalation design is adopted, and the selection of MTD (Maximum Tolerated Dose) is finally determined according to the occurrence of DLT (Dose-Limiting Toxicity). There are three escalating dose groups: A, B, and C, with 3 subjects in each group. The groups are sequentially conducted from low dose to high dose according to the principle of dose escalation. Group A: intravenous infusion of 2 × 10⁶ cells/kg body weight once; Group B: intravenous infusion of 2 × 10⁶ cells/kg body weight, once a week for 2 times; Group C: intravenous infusion of 2.0 × 10⁶ cells/kg body weight, once a week for 4 times. It is expected to enroll 9 - 18 subjects in the dose escalation phase. Based on the above trial results, investigators will determine a specific dose test group (one of A, B, and C) and expand the sample size by 6 subjects.\n\nSafety assessments will be carried out during the treatment period, including vital signs, physical examinations, laboratory tests, etc. After the last treatment, safety assessments and safety follow-up will be conducted for 24 weeks. The first 8 weeks will be one visit period per week, and 9 - 24 weeks will be one visit period per month.', 'detailedDescription': 'Primary Endpoint Safety endpoint: The incidence and severity of adverse events and serious adverse events (mainly including infusion reactions, embolism events, viral infections, abnormalities in liver and kidney functions, abnormalities in coagulation function, etc.) within 24 weeks after MSC infusion (based on the NCI CTCAE 5.0 standard).\n\nSecondary Endpoints Response rate within 4 weeks/8 weeks after the first MSC infusion, including CR rate, PR rate, and OR rate; Median time for each lineage of blood cells from the first MSC infusion to the first achievement of CR/PR.\n\nDuration of response (DOR) for each lineage of blood cells;\n\nCR criteria (no red blood cell/platelet transfusion for at least 7 days and meeting the standards in two consecutive tests):\n\nHemoglobin (Hb) ≥ 100 g/L (for adults) or ≥ the lower limit of age-corrected normal value; Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count (PLT) ≥ 100 × 10⁹/L.\n\nPR criteria: Meeting any of the following conditions (no red blood cell/platelet transfusion for at least 7 days and meeting the standards in two consecutive tests)\n\nNeutrophils: The absolute value increases by ≥ 0.5 × 10⁹/L compared with the baseline; Platelets: The absolute value increases by ≥ 10 × 10⁹/L compared with the baseline; Hemoglobin: The absolute value increases by ≥ 15 g/L compared with the baseline.\n\nOther Endpoints Changes in in vivo immune indicators and inflammatory indicators after the infusion of umbilical cord blood-derived mesenchymal stem cells (changes in ferritin, C-reactive protein, LDH, lymphocyte subsets, quantitative immunoglobulin, and cytokines).\n\nStudy Population Inclusion Criteria\n\nPatients must meet the following criteria to be enrolled in this study:\n\nPatients voluntarily participate in this study and sign an informed consent form; Aged ≥ 18 years, regardless of gender; Patients with acute lymphoblastic leukemia, lymphoma, or multiple myeloma who still have severe cytopenia 3 weeks after CAR-T reinfusion (meeting any of the following conditions: neutrophil count ≤ 1 × 10⁹/L; platelet count ≤ 30 × 10⁹/L; hemoglobin ≤ 70 g/dL).\n\nECOG performance status ≤ 2; Predicted survival time ≥ 6 months; For female patients of childbearing potential, the pregnancy test result must be negative. Female patients of childbearing potential and male patients must use highly effective contraceptive measures during the study period and within 4 months/6 months after stopping treatment, respectively;\n\nExclusion Criteria\n\nPatients with any of the following conditions are prohibited from enrolling in this study:\n\nAfter CAR-T reinfusion, other anti-tumor treatments that may affect the hematopoietic system or blood cell count (including but not limited to chemotherapy, radiotherapy, targeted therapy, immunotherapy, or hematopoietic stem cell transplantation) have been received within 1 month before the screening period; There is still obvious tumor cell infiltration in the bone marrow during the screening period (the proportion of leukemia cells in the bone marrow morphology of ALL is greater than 5%, MRD is positive by bone marrow flow cytometry in MM and lymphoma patients, or lymphoma/clonal plasma cell infiltration is visible by bone marrow pathological immunohistochemistry).\n\nWithin 1 week before the first administration, there are the following situations: infection with unstable hemodynamics (requiring vasoactive drug support); deep fungal infection confirmed by imaging or microbiology (such as invasive aspergillosis, bloodstream infection, etc.); Pneumocystis jirovecii pneumonia, active tuberculosis, viremia (cytomegalovirus, parvovirus B19, etc.) and viral pneumonia (cytomegalovirus, COVID-19, influenza virus, adenovirus, parainfluenza virus, etc.), and other serious infections that the investigator judges may affect hematopoiesis; Creatinine and blood urea nitrogen ≥ 1.5 times the upper limit of normal (ULN); Alanine aminotransferase or aspartate aminotransferase ≥ 3 times ULN; total bilirubin ≥ 1.5 times ULN; Other serious and/or uncontrolled diseases and conditions that the investigator deems may affect participation in the study, including but not limited to: having serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, II - III degree atrioventricular block, etc., QTcF interval on electrocardiogram \\> 480 ms; New York Heart Association (NYHA) cardiac function class III - IV, uncontrolled diabetes (HbA1c \\> 9%), refractory hypertension, chronic obstructive pulmonary disease (FEV1 \\< 50% predicted value), etc.; Patients with a history of arteriovenous thrombosis or atherosclerosis; Positive anti-human immunodeficiency virus antibody or anti-Treponema pallidum specific antibody; positive hepatitis B surface antigen (HBsAg), or positive hepatitis B core antibody with HBV-DNA greater than the upper limit of normal, or HCV-RNA \\> upper limit of normal for hepatitis C.\n\nPrevious or current malignant solid tumors (except for cured non-invasive basal cell or squamous cell skin cancer and/or other cured carcinoma in situ; except for other malignant tumors that have achieved clinical cure for \\> 5 years and have not recurred within 5 years); Within 6 months after allogeneic hematopoietic stem cell transplantation or donor cell chimerism rate ≤ 95% or presence of grade II or above active acute GVHD or moderate or above chronic GVHD; Live vaccines have been administered within 4 weeks before the first administration, or any live vaccines are planned to be administered during the study period; Pregnant or lactating female patients; Patients with mental disorders; Participated in any other investigational drug study (including vaccine studies) or exposed to other investigational drugs within 4 weeks or 5 half-lives (whichever is longer) before the first administration; Patients who refuse to sign the consent form; Other situations judged by the investigator as unsuitable for inclusion in the study.\n\nStudy Treatment Usage and Dosage of Umbilical Cord Blood-Derived Mesenchymal Stem Cells Cell preparation name: Umbilical cord blood-derived mesenchymal stem cell injection (UCell Life Science Development Co., Ltd.). The main component is mesenchymal stem cells derived from human umbilical cord blood cultured in vitro. Each bag contains 100 ml and 1.0 × 10⁸ mesenchymal stem cells. The production and preparation process meets the corresponding standards. Before the release of the final MSC cell product, UCell Life Science Development Co., Ltd. conducts quality control tests on the final product.\n\nUsage: Sequentially divided into three escalating dose groups: A, B, and C, with 3 subjects in each group: Group A: intravenous infusion at a dose of 2 × 10⁶ cells/kg body weight, once a week for 1 time; Group B: intravenous infusion at a dose of 2 × 10⁶ cells/kg body weight, once a week for 2 times; Group C: intravenous infusion at a dose of 2.0 × 10⁶ cells/kg body weight, once a week for 4 times. All patients use 5 mg dexamethasone before infusion to prevent infusion reactions.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria\n\nPatients must meet all the following criteria to be enrolled in this study:\n\nVoluntarily participate in the study and sign the informed consent form; Aged ≥ 18 years, regardless of gender; 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; ECOG performance status score ≤ 2; Estimated survival time ≥ 6 months; 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.\n\nExclusion Criteria\n\nPatients with any of the following conditions are prohibited from enrolling in this study:\n\nHaving 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; 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); 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; Serum creatinine or blood urea nitrogen ≥ 1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times ULN; total bilirubin ≥ 1.5 times ULN; 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.; History of arteriovenous thrombosis or atherosclerosis; 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; 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); 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); Having received a live vaccine within 4 weeks before the first dose administration, or planning to receive any live vaccine during the study period; Pregnant or lactating female patients; Patients with mental disorders; 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; Patients who refuse to sign the informed consent form; Other conditions deemed unsuitable for study inclusion by the investigator."}, 'identificationModule': {'nctId': 'NCT07212335', 'acronym': 'MSC-ICAHT', 'briefTitle': 'Safety and Efficacy of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in the Treatment of Long-Term Cytopenia After CAR-T Therapy', 'organization': {'class': 'OTHER', 'fullName': 'Institute of Hematology & Blood Diseases Hospital, China'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'IIT2025028'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'MSC', 'description': 'Mesenchymal stem cells: intravenous infusion, 2×10⁶ cells/kg body weight/week (once weekly), with 1 to 4 administrations based on different dosage groups.', 'interventionNames': ['Biological: Mesenchymal Stem Cell Infusion']}], 'interventions': [{'name': 'Mesenchymal Stem Cell Infusion', 'type': 'BIOLOGICAL', 'description': 'Mesenchymal stem cells: intravenous infusion, 2×10⁶ cells/kg body weight/week (once weekly), with 1 to 4 administrations based on different dosage groups.', 'armGroupLabels': ['MSC']}]}, 'contactsLocationsModule': {'locations': [{'zip': '300020', 'city': 'Tianjin', 'country': 'China', 'contacts': [{'name': 'Zhenzhen Wang', 'role': 'CONTACT', 'email': 'wangzhenzhen@ihcams.ac.cn', 'phone': '22-23608095'}], 'facility': 'Chinese Academy of Medical Sciences Hospital of Hematology (Chinese Academy of Medical Sciences Institute of Hematology)', 'geoPoint': {'lat': 39.14222, 'lon': 117.17667}}], 'centralContacts': [{'name': 'Zhenzhen Wang', 'role': 'CONTACT', 'email': 'wangzhenzhen@ihcams.ac.cn', 'phone': '22-23608095'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP'], 'timeFrame': '12 months to 36 months after study completion', 'ipdSharing': 'YES', 'description': 'Researchers qualified can request the dataset, including de-identified individual subject data. Data may be requested from PI from 12 months to 36 months after study completion.', 'accessCriteria': 'Upon request to PI'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Institute of Hematology & Blood Diseases Hospital, China', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}