Anti-BCMA CAR‑T therapy for adults with relapsed or refractory multiple myeloma

Phase I/II Open-label Study Evaluating The Safety And Efficacy of Anti BCMA CAR-T Cell Therapy in Adults With R/ R Multiple Myeloma

This tests whether a patient's own engineered anti-BCMA CAR‑T cells can help adults whose multiple myeloma has come back or stopped responding to treatment and whether the approach is safe.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Minsk Scientific-Practical Center for Surgery, Transplantation and Hematology (other gov)
• Drugs / interventions: tocilizumab, CAR-T, chemotherapy, radiation, Methotrexate, cyclophosphamide, fludarabine, immunotherapy
• Locations: 1 site (Minsk)
• Trial ID: NCT07477912 on ClinicalTrials.gov

What this trial studies

This interventional Phase 1/2 program uses locally manufactured, second‑generation humanized autologous anti‑BCMA CAR‑T cells delivered as a single infusion after leukapheresis and lymphodepleting chemotherapy (fludarabine and cyclophosphamide). Phase 1 focuses on preliminary safety and tolerability, monitoring for cytokine release syndrome (CRS), immune effector cell‑associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis (HLH), infections, late immune complications and cytopenias, with exploratory CAR‑T pharmacokinetics. Phase 2 measures clinical efficacy by overall response rates (PR, VGPR, CR, sCR) and collects secondary outcomes including duration of response, progression‑free survival, and overall survival. Treatment and follow‑up are performed at the Minsk Scientific and Practical Center for Surgery, Transplantology, and Hematology.

Who should consider this trial

Good fit: Adults aged 18 or older with relapsed or refractory multiple myeloma after at least two prior lines of therapy who are refractory to proteasome inhibitors and immunomodulators, have ECOG 0–2, adequate organ and bone marrow function, and no active Grade 2–4 GVHD are ideal candidates.

Not a fit: People with inadequate organ or marrow function, active significant GVHD, very poor performance status, or other exclusionary medical conditions are unlikely to benefit or be eligible for this protocol.

Why it matters

Potential benefit: If successful, this therapy could produce deep remissions in some adults with relapsed or refractory multiple myeloma using their own engineered immune cells.

How similar studies have performed: Other anti‑BCMA CAR‑T products have produced high response rates in heavily pretreated multiple myeloma but are also associated with significant risks such as CRS and neurotoxicity.

Eligibility criteria

Inclusion Criteria:

1. Male or female, aged ≥18 years.
2. Willing and able to give written, informed consent.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.
4. Relapsed or refractory multiple myeloma according to IMWG criteria with two previous lines of therapy and resistance to proteosome inhibitors and immunomodulators.
5. Adequate organ system function including

   \- Creatinine clearance ≥30 cc/min.

   \- Serum alanine aminotransferase / aspartate aminotransferase ≤2.5 x upper limit of normal (ULN).

   \- Total bilirubin ≤1.5 x ULN, except in subjects with Gilbert's syndrome.

   \- Left ventricular ejection fraction (LVEF) ≥50% (by echocardiogram \[ECHO\] or

   \- Baseline oxygen saturation \>92% on room air and ≤Grade 1 dyspnoea.
6. Have no active GVHD (Grade 2-4)
7. Adequate bone marrow (BM) function

   * Absolute neutrophil count ≥1.0 × 10\^9/L.
   * Absolute lymphocyte count ≥0.3 × 10\^9/L (at enrolment and prior to leukapheresis).
   * Haemoglobin ≥80 g/L.
   * Platelets ≥50 × 10\^9/L

Exclusion Criteria:

1. Females who are pregnant or lactating.
2. History or presence of clinically relevant CNS pathology such as epilepsy, paresis, aphasia, stroke within prior 3 months, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis.
3. Patients with active CNS involvement by malignancy. Patients with history of central nervous system (CNS) involvement with malignancy may be eligible if CNS disease has been effectively treated and provided treatment was at least 4 weeks prior to enrolment (at least 8 weeks prior to CAR-T infusion).
4. Clinically significant, uncontrolled heart disease or a recent (within 12 months) cardiac event.
5. Active bacterial, viral or fungal infection requiring systemic treatment. Active or latent hepatitis B infection or hepatitis C infection. Testing positive for human immunodeficiency virus, human T cell lymphotropic virus (HTLV1 and 2) or syphilis.
6. History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months.

6\. Evidence of active pneumonitis on chest computed tomography (CT) scan at screening or history of drug-induced pneumonitis, idiopathic pulmonary fibrosis, organising pneumonia, or idiopathic pneumonitis.

7\. History of other malignant neoplasms unless disease free for at least 24 months (carcinoma in situ, non-melanoma skin cancer, breast or prostate cancer on hormonal therapy allowed).

8\. The following medications are excluded:

* Steroids: Therapeutic doses of corticosteroids within 7 days of leukapheresis or 72 hours prior to CAR-T administration. However, physiological replacement, topical, and inhaled steroids are permitted.
* Immunosuppression: Immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis or CAR-T cells infusion.
* Cytotoxic chemotherapies within 1 week of CAR-T cellsinfusion and 1 week prior to leukapheresis.
* Granulocyte-colony stimulating factor less than 14 days prior to leukapheresis.
* Live vaccine ≤4 weeks prior to enrolment.
* Prophylactic intrathecal therapy: Methotrexate within 4 weeks and other intrathecal chemotherapy (e.g. Ara-C) within 2 weeks prior to starting pre-conditioning chemotherapy.

Prior limited radiation therapy within 2 weeks of CAR-T cells infusion. 9. Prior anti BCMA therapy 10. Known allergy to albumin, dimethyl sulphoxide (DMSO), cyclophosphamide or fludarabine or tocilizumab.

11\. Any other condition that in the Investigator's opinion would make the patient unsuitable for the clinical trial.

Where this trial is running

Minsk

• State Institution Minsk Scientific and Practical Center for Surgery, Transplantology, and Hematology — Minsk, Belarus (RECRUITING)

Study contacts

• Principal investigator: Mikhail Uss, MD — State Institution Minsk Scientific and Practical Center for Surgery, Transplantology, and Hematology, Minsk, 220087
• Study coordinator: Mikhail Uss, MD

Conditions: Multiple Myeloma Refractory, CAR-T therapy, multiple myeloma