Anti BCMA CAR- T Cell Therapy for Adults With Relapsed or Refractory Multiple Myeloma (MSTH-CAR001)

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

The mail purpose of this study is to estimate the safety and the efficacy of anti-BCMA CAR- T cell immunotherapy for adults with relapsed or refractory multiple myeloma

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma Refractory
• Intervention / Treatment: Biological: anti BCMA CAR-T cells

Detailed Description

Locally manufactured second generation autologous humanized anti-BCMA cells are used for immunotherapy. Protocol treatment includes leukapheresis in order to harvest T cells, lymphodepleting conditioning (fludarabine 30 mg/m2+ cyclophosphamide 300 mg/2(days -5-3)) followed by one anti (day 0) BCMA CAR-T cell infusion.

The Main research objectives of the Phase I:

To preliminarily explore the safety (incidence of CRS, ICANS, HLH, infections, late ICAHT, p arkinsonism and cytopenias) and tolerability.

The Secondary research objectives of the Phase I:

To explore the pharmacokinetics of CAR-T cells.

The Main research objectives of the Phase II:

Overall response rate, including partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response(sCR) rates.

The Secondary research objectives of the Phase II:

Duration of response (DOR). Progression-free survival rates. Overall survival rates.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Mikhail Uss, MD; Phone Number: +375291362230; Email: mikhail.uss@mail.ru

Study Locations

• Belarus
  • Minsk, Belarus, 220087
    • Recruiting
    • State Institution Minsk Scientific and Practical Center for Surgery, Transplantology, and Hematology
    • Contact: Mikhail Uss, MD; Phone Number: +375291362230; Email: mikhail.uss@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anti BCMA CAR-T cell-immunotherapy	Biological: anti BCMA CAR-T cells; Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with doses from 50 x 10⁶ to 250 x 10⁶ anti BCMA CAR-T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I. Safety	Number of Participants With Grade 3-5 Toxicities. Adverse events will be graded according to the CTCAE v5.0, ICAHT and ASCTC.	1 month post CAR-T cells infusion
Phase II. Overall response rate	partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR) rates according to IMVG criteria	12 months post CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I. duration of expansion of CAR-T cells	To explore the pharmacokinetics of CAR-T cells: - duration of expansion of CAR-T cells by flow cytometry - duration of cell detection in peripheral blood (days)	12 months post CAR-T cells infusion
Phase II. Efficacy: Overall survival rates	Overall survival rates	3 years post CAR-T cells infusion
Phase II. Progression-free survival rates	progression-free survival time	3 years post CAR-T cells infusion
Phase II. Duration of response	duration of response	3 years post CAR-T cells infusion
Phase I. Peak of expansion of CAR-T cells	- peak of expansion of CAR-T cells (cells/µl) - The day of maximum cell concentration in peripheral blood and bone marrow (day)	1 month post CAR-T cells infusion

Collaborators and Investigators

• Sponsor: Minsk Scientific-Practical Center for Surgery, Transplantation and Hematology
• Investigators: Principal Investigator: Mikhail Uss, MD, State Institution Minsk Scientific and Practical Center for Surgery, Transplantology, and Hematology, Minsk, 220087

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: February 24, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: multiple myeloma; CAR-T therapy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma
• Other Study ID Numbers: 123.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No