Nanobody-based Biepitope CAR-T Cells Targeting BCMA in the Treatment of R/RMM

NCT06503107 | Recruiting Phase 1

• 1 other identifier: biepitope BCMA CAR-T
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

To explore the safety and efficacy of nanobody-based BCMA-targeting biepitope CAR-T cells in the treatment of relapsed/refractory multiple myeloma，this study will be conducted in multiple study centers, with 60 patients openly enrolled to receive CAR-T cell therapy. Patients participating in clinical trials will be tested and evaluated for treatment safety, efficacy, duration of response, and long-term survival.

Conditions

Multiple Myeloma

Keywords

CAR-T; BCMA; Relapsed / Refractory multiple myeloma

Outcome Measures

Primary Outcomes (6)

• Incidence of Treatment-related Adverse Events

  Therapy-related adverse events (AE), including severe adverse events (SAE) and laboratory outliers with clinical significance, will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).

  within 3 years after infusion

• Overall response rate (ORR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM

  Disease overall response rate (ORR) will be assessed from CAR-T cell infusion to death or last follow-up (censored). The rates of stringent complete response (sCRs), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR) will be assessed from CAR T cell infusion to death or last follow-up (censored). ORR will be assessed from CAR T cell infusion to death or last follow-up.

  within 3 years after infusion

• The rates of complete response (CR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM

  CR will be assessed from CAR-T cell infusion to death or last follow-up (censored).

  within 3 years after infusion

• Very good partial response (VGPR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM

  VGPR will be assessed from CAR-T cell infusion to death or last follow-up (censored).

  within 3 years after infusion

• Partial response rate (PR) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM

  PR will be assessed from CAR-T cell infusion to death or last follow-up (censored).

  within 3 years after infusion

• Stable diseases (SD) of nanobody-based biepitope CAR-T cells targeting BCMA in R/R MM

  SD will be assessed from CAR-T cell infusion to death or last follow-up (censored).

  within 3 years after infusion

Secondary Outcomes (3)

• Overall survival (OS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma

  within 3 years after infusion

• Progression-free survival (PFS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma

  within 3 years after infusion

• Event-free survival (EFS) of nanobody-based biepitope CAR-T cells targeting BCMA in Relapsed/Refractory multiple myeloma

  within 3 years after infusion

Other Outcomes (1)

• In vivo expansion and survival of nanobody-based biepitope CAR-T cells targeting BCMA

  within 3 years after infusion

Study Arms (1)

Effective of nanobody-based biepitope BCMA-targeting CAR-T cells

EXPERIMENTAL

The recommended reinfusion dose of biepitope BCMA-targeting CAR-T cells in this trial is: 1 × 10\^6/kg, 2 × 10\^6/kg CAR-T cells.

Drug: Nanobody-based biepitope BCMA-targeting CAR-T cells

Interventions

Nanobody-based biepitope BCMA-targeting CAR-T cells DRUG

Each patient will receive nanobody-based biepitope BCMA-targeting CAR-T cell by intravenous infusion on day 0.

Effective of nanobody-based biepitope BCMA-targeting CAR-T cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
• Aged ≥ 18 years and ≤ 75 years.
• Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG 2014).
• Diagnosed as relapsed/refractory disease or primary refractory disease; relapse is defined as disease progression within 60 days of the most recent treatment with three or more lines of therapy with different mechanisms of action; refractory is defined as failure to achieve MR or above efficacy with prior treatment and disease progression with recent treatment, or disease progression within 60 days of treatment.
• Flow cytometry or immunohistochemistry showed positive BCMA expression in myeloma cells.
• Have not been treated with antibody-based drugs within 2 weeks prior to cell therapy.
• ECOG score 0-2 points.
• HGB≥70g/L，PLT≥30×10\^9/L.
• Liver, kidney and cardiopulmonary functions meet the following requirements:
• Serum creatinine ≤ 1.5× ULN or creatinine clearance (Cockcroft-Gault) \>30 ml/min；
• Left ventricular ejection fraction (LVEF) ≥50%,
• Baseline peripheral oxygen saturation \> 90%;
• Total bilirubin ≤ 1.5×ULN; ALT and AST ≤2.5×ULN.

You may not qualify if:

• Previous diagnosis and treatment of other malignancies within 3 years;
• Presence of one of the following cardiac criteria: atrial fibrillation; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary QT prolongation, as judged by the investigator. Echocardiogram LVSF \<30% or LVEF \<50%; Clinically significant pericardial effusion; Cardiac insufficiency NYHA (New York Heart Association) III or IV (absence of this symptom confirmed by echocardiography within 12 months of treatment);
• Patients with active GVHD;
• Patients with a history of severe pulmonary impairment disease;
• Combined with other malignant tumors in the advanced stage;
• Co-infection with severe or persistent infection that cannot be effectively controlled;
• Combined with severe autoimmune disease or congenital immunodeficiency;
• Active hepatitis (hepatitis B virus deoxyribonucleic acid \[HBV-DNA ≥ 500 IU/ml and abnormal liver function\] or hepatitis C antibody \[HCV-Ab\] positive, HCV-RNA above the lower limit of detection of the analytical method and abnormal liver function);
• Human immunodeficiency virus (HIV) infection or syphilis infection;
• Patients with a history of severe allergy to biological products (including antibiotics);
• Patients with central nervous system disorders such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, etc;
• Pregnant or Lactating Women; Patients and his or her spouses have a fertility plan within 12 months after CAR-T cell infusion;
• Other conditions considered inappropriate by the researcher.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Hebei Taihe Chunyu Biotechnology Co., Ltd: collaborator
• Huazhong University of Science and Technology Union Shenzhen Hospital: collaborator
• The Seventh Affiliated Hospital of Sun Yat-sen University: collaborator

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Related Publications (4)

• Cohen AD, Garfall AL, Stadtmauer EA, Melenhorst JJ, Lacey SF, Lancaster E, Vogl DT, Weiss BM, Dengel K, Nelson A, Plesa G, Chen F, Davis MM, Hwang WT, Young RM, Brogdon JL, Isaacs R, Pruteanu-Malinici I, Siegel DL, Levine BL, June CH, Milone MC. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest. 2019 Mar 21;129(6):2210-2221. doi: 10.1172/JCI126397.

  PMID: 30896447 BACKGROUND

• Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, Stewart AK, Hari P, Htut M, Lesokhin A, Deol A, Munshi NC, O'Donnell E, Avigan D, Singh I, Zudaire E, Yeh TM, Allred AJ, Olyslager Y, Banerjee A, Jackson CC, Goldberg JD, Schecter JM, Deraedt W, Zhuang SH, Infante J, Geng D, Wu X, Carrasco-Alfonso MJ, Akram M, Hossain F, Rizvi S, Fan F, Lin Y, Martin T, Jagannath S. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021 Jul 24;398(10297):314-324. doi: 10.1016/S0140-6736(21)00933-8. Epub 2021 Jun 24.

  PMID: 34175021 BACKGROUND

• Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, Steinberg SM, Stroncek D, Tschernia N, Yuan C, Zhang H, Zhang L, Rosenberg SA, Wayne AS, Mackall CL. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015 Feb 7;385(9967):517-528. doi: 10.1016/S0140-6736(14)61403-3. Epub 2014 Oct 13.

  PMID: 25319501 RESULT

• Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ, Brudno JN, Stetler-Stevenson M, Feldman SA, Hansen BG, Fellowes VS, Hakim FT, Gress RE, Kochenderfer JN. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood. 2016 Sep 29;128(13):1688-700. doi: 10.1182/blood-2016-04-711903. Epub 2016 Jul 13.

  PMID: 27412889 RESULT

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Mei Heng, M.D., Ph.D

CONTACT

027-8572600; hmei@hust.edu.cn

Yun Kang

CONTACT

17362995329; cloudykang@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: : Proferssor, Cheif Doctor

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: July 16, 2024
• Study Start: April 23, 2024
• Primary Completion: April 18, 2026
• Study Completion (Estimated): October 18, 2026
• Last Updated: July 16, 2024

Record last verified: 2024-07

Locations

CN (1)