Autologous stem‑cell transplant plus BCMA CAR‑T for ultra‑high‑risk multiple myeloma

Clinical Study on the Safety and Efficacy of Autologous Hematopoietic Stem Cell Transplantation Combined With BCMA-CAR-T in the Treatment of Ultra-high Risk Multiple Myeloma

This test combines an autologous stem‑cell transplant with BCMA CAR‑T therapy to see if it helps adults (18–70) with ultra‑high‑risk multiple myeloma who are eligible for transplant.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: car-t, prednisone, CART
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07109323 on ClinicalTrials.gov

What this trial studies

This single‑center, prospective Phase 1/2 study at the Institute of Hematology & Blood Diseases Hospital in Tianjin tests combining autologous hematopoietic stem‑cell transplantation (ASCT) with BCMA‑targeted CAR‑T therapy in patients with ultra‑high‑risk multiple myeloma. Eligible adults (18–70) must be suitable for ASCT and meet predefined UHR criteria such as high‑risk cytogenetics, primary refractory disease, early progression, or plasma cell leukemia. Participants will undergo standard ASCT followed by infusion of BCMA CAR‑T cells, with close monitoring for safety, tolerability, and treatment responses over the follow‑up period. The study will measure adverse events and response rates to determine whether the combination can deepen and prolong remissions in this high‑risk population.

Who should consider this trial

Good fit: Adults aged 18–70 with ultra‑high‑risk multiple myeloma who are judged suitable for autologous stem‑cell transplantation and who meet the study's UHR criteria (high‑risk cytogenetics, primary refractory, early progression, or plasma cell leukemia).

Not a fit: Patients who are older than 70, not eligible for ASCT, have significant comorbidities, or who have standard‑risk multiple myeloma are unlikely to be eligible or to benefit from this combination approach.

Why it matters

Potential benefit: If successful, the combination could produce deeper and longer remissions than ASCT alone for patients with ultra‑high‑risk multiple myeloma.

How similar studies have performed: BCMA‑targeted CAR‑T therapies have shown high response rates in relapsed/refractory multiple myeloma, but integrating CAR‑T with autologous transplant in newly treated ultra‑high‑risk patients is a relatively new approach with limited prior data.

Eligibility criteria

Inclusion Criteria:

Subjects must meet all of the following criteria to be enrolled:

Ultra high risk mm (UHR-MM), 18-70 years old, suitable for ASCT. And meet any of the following definitions of UHR-MM: 1) cytogenetic ultra-high risk, which meets any of the following conditions, including: del(17p)≥60%； Two or more cytogenetic features: TP53 mutation, del (17p) or p53 deletion, t (4; 14), t (14; 16), t (14; 20), 1q21 gain or amplification, 1p deletion, myc translocation (deletion or copy number abnormality: ≥ 20% is positive; translocation: ≥ 10% is positive); 2) Primary refractory (first-line induction therapy based on standard three drug combination: 2 courses \< Mr, 4 courses \< PR); 3) Early progression (the best first-line treatment response of the regimen based on the standard three drug combination is maintained for less than 6 months); 4) Plasma cell leukemia (meeting the diagnostic criteria of mm at the initial diagnosis, and the proportion of peripheral plasma cells ≥ 5%); 5) Non paraosseous extramedullary infiltration; 6) R2-iss-iv /mpss-iv.

1. The subjects voluntarily participated in the study and signed the informed consent form (ICF) by themselves or their legal guardians;
2. The subject must have proper organ function and meet all the following inspection results:

Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Creatinine clearance (CrCl) (Cockcroft Gault formula) ≥ 40ml/min; Prothrombin time (PT) ≤ 1.5 × ULN, partial prothrombin time (APTT) \< 1.5 × ULN, international normalized ratio (INR) \< 1.5 × ULN; Hemoglobin (HB) ≥ 60g/L; Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L (no growth factors such as granulocyte colony-stimulating factor \[G-CSF\] received within 7 days before laboratory examination in screening period); Absolute lymphocyte count (ALC) ≥ 0.5 × 10\^9/L; Platelet (PLT) ≥ 50 × 10\^9/L (no platelet transfusion within 7 days before laboratory examination in screening period); Left ventricular ejection fraction (LVEF) ≥ 45%; Blood oxygen saturation (SpO2) ≥ 92%; (3) The ECoG score is 0-1. See Appendix V for ECOG score; (4) Estimated survival ≥ 3 months; (5) The pregnancy test of fertile female subjects should be negative and not within the lactation period; Both female and male subjects need to take effective contraceptive tools or drugs within 24 months after cell infusion.

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Exclusion Criteria:Subjects who have one or more of the following cannot be selected for this study:

1. Have a history of allergy to any component in cell products;
2. Serious heart disease, including but not limited to:

   Myocardial infarction, cardiac angioplasty or stent implantation within 6 months before signing ICF Unstable angina Severe arrhythmia History of severe non ischemic cardiomyopathy Congestive heart failure (New York Heart Association \[nyha\] class III or IV), and the NYHA score is shown in Appendix II
3. History of autologous / allogeneic hematopoietic stem cell transplantation;
4. Stroke or seizure within 6 months before signing ICF;
5. Have autoimmune disease, immune deficiency or other diseases requiring immunosuppressant treatment;
6. Within 3 years before signing the ICF, patients with malignant tumors other than multiple myeloma, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, breast ductal carcinoma in situ after radical surgery, and carcinoma in situ in other parts one year after radical surgery, and there has been no treatment and no recurrence in the screening period Signs;
7. The presence of uncontrolled active infection;
8. Unstable systemic diseases judged by the investigator: including but not limited to serious liver, kidney or metabolic diseases requiring drug treatment;
9. Any of the following conditions exist within 1 week before lymphocyte collection:

   The detection value of hepatitis B virus (HBV) DNA in peripheral blood was higher than the lower limit of detection Hepatitis C virus (HCV) antibody positive and peripheral HCV-RNA positive Human immunodeficiency virus (HIV) antibody positive Syphilis antigen or antibody positive Cmv-dna positive
10. More than 5mg/d prednisone (or equivalent amount of other corticosteroids) was applied within 1 week before lymphocyte collection Vegan);
11. Have used any car-t cell products or other genetically modified T cell therapies;
12. Received BCMA targeted therapy;
13. Have a history of live vaccination within 4 weeks before signing ICF;
14. Have a history of alcohol abuse, drug abuse or mental illness;
15. Other researchers consider it inappropriate to participate in this study. -

Where this trial is running

Tianjin, Tianjin Municipality

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

Study contacts

• Principal investigator: Dehui Zou — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Dehui Zou

Conditions Ultra High Risk mm, 18-70 Years Old, Suitable for ASCT. And Meet Any of the Following uhr-mm Definitions; Cytogenetics Ultra High Risk; Primary Refractory; Early Progression; Plasma Cell Leukemia; Non Paraosseous Extramedullary Infiltration; R2-ISS-IV /MPSS-IV