CAR-T in Relapsed/Refractory Multiple Myeloma

NCT07689058 | Recruiting Phase 2 DMC

• 1 other identifier: BCMA-CAR-PK-01/Protocol/1.0
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

The treatment options for multiple myeloma have evolved significantly over the years, providing patients with a range of therapies tailored to their specific circumstances. The choice of treatment often hinges on various factors, including the aggressiveness of the disease, individual prognostic indicators like genetic markers, the overall physical condition of the patient, and any pre-existing health issues that may affect treatment decisions. Current therapeutic strategies include several classes of drugs, each working through different mechanisms. Proteasome inhibitors (PIs) disrupt the protein degradation process within myeloma cells, thereby promoting their death. Immunomodulatory drugs (IMiDs) modulate the immune system and inhibit tumor growth by enhancing the body's natural anti-cancer responses. Monoclonal antibodies specifically target cancer cells, marking them for destruction by the immune system. In cases where patients are eligible, autologous stem cell transplantation remains a viable option, offering the potential for long-term remission by replacing damaged bone marrow with healthy stem cells from the patient's own body. Despite these advancements, multiple myeloma continues to present significant challenges, as it often recurs even after initial successful treatment and remains an incurable disease. This highlights the urgent need for innovative therapeutic strategies that can effectively address resistance to existing treatments, ultimately aiming to improve patient outcomes and survival rates.

Conditions

Multiple Myeloma Refractory; Multiple Myeloma in Relapse

Keywords

CAR-T, Multiple Myeloma, Relapsed, Refractory

Outcome Measures

Primary Outcomes (1)

• Assess Safety /tolerability and feasibility of manufacturing and delivering the product

  incidence/severity of AEs including CRS/ICANS (ASTCT grading), DLTs through Day +28

  From enrolment to 1 years after infusion of the product

Study Arms (1)

CAR-T arm

OTHER

6.2. Screening Phase During the Screening period, all participants will be asked to provide written consent for study participation and will be screened for study eligibility within 28 days before apheresis. Safety criteria that must be met before starting apheresis are presented in Section 8.1.1. If an assessment was performed as part of the participant's routine clinical evaluation and not specifically for this study, it does not need to be repeated after signed informed consent has been obtained, provided the assessments fulfill the study requirements and are performed within the specified timeframe before the first dose of study treatment. Retesting of abnormal screening values that lead to exclusion is allowed only once during the screening phase (to reassess eligibility). The last result obtained before apheresis will be used to determine eligibility. Subjects who do not meet all inclusion criteria or who meet an exclusion criterion may, at the discretion of the investigator,

Biological: CAR-T

Interventions

CAR-T BIOLOGICAL

CAR-T therapy will be given

CAR-T arm

Eligibility Criteria

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

You may qualify if:

• Male and female participants of age 18 years and above.
• Patients with a confirmed diagnosis of multiple myeloma according to IMWG diagnostic criteria.
• Received at least 3 prior multiple myeloma treatment lines of therapy or are double refractory to an IMiD and PI (refractory multiple myeloma as defined by IMWG consensus criteria). Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single line of therapy.
• Measurable disease at Screening as per IMWG criteria.
• ECOG Performance Status grade of 0 to 2.
• Adequate organ function: ANC/platelets thresholds (unless cytopenias attributable to MM), LVEF ≥45%, adequate oxygenation; hepatic/renal criteria specified in Section 10.
• Negative pregnancy test for women of childbearing potential; agreement to effective contraception.
• Patients giving written informed consent to participate in the study after a full understanding of the implications and constraints of the study protocol.
• Understand the content of the ICF, and voluntarily sign the ICF (If the participant is unable to sign the ICF on their own due to illiteracy, an impartial witness is needed).
• The subject can understand the research process and is willing and able to comply with all research proposals and other requirements of the study.
• Willing and able to adhere to the prohibitions and restrictions specified in this protocol.

You may not qualify if:

• \. Patients who will meet any of the following criteria will not be eligible to participate in the study.
• Prior treatment with CAR-T therapy directed at any target. Any therapy that is targeted to BCMA.
• Known active, or prior history of central nervous system (CNS) involvement, or exhibits clinical signs of meningeal involvement of multiple myeloma.
• Stroke or seizure within 6 months of signing the ICF.
• Uncontrolled active infection, including uncontrolled bacterial or fungal infection; active uncontrolled HBV/HCV/HIV.
• Clinically significant cardiac disease (e.g., NYHA III/IV, recent MI), or severe pulmonary disease.
• Recent allogeneic HSCT with active GVHD or ongoing immunosuppression.
• Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within 1 year after receiving study treatment.
• Any other circumstances that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to understand informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Sponsors & Collaborators

• Dr. Zaineb Akram: lead

Study Sites (2)

National University of Medical Sciences, Clinical Trial Unit

Rawalpindi, Punjab Province, 46000, Pakistan

RECRUITING

National University of Medical Sciences, Clinical Trial Unit

Rawalpindi, Punjab Province, 46000, Pakistan

RECRUITING

Related Publications (6)

• Sommer C, Boldajipour B, Kuo TC, Bentley T, Sutton J, Chen A, Geng T, Dong H, Galetto R, Valton J, Pertel T, Juillerat A, Gariboldi A, Pascua E, Brown C, Chin SM, Sai T, Ni Y, Duchateau P, Smith J, Rajpal A, Van Blarcom T, Chaparro-Riggers J, Sasu BJ. Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma. Mol Ther. 2019 Jun 5;27(6):1126-1138. doi: 10.1016/j.ymthe.2019.04.001. Epub 2019 Apr 8.

  PMID: 31005597 BACKGROUND

• Durie BG, Miguel JF, Blade J, Rajkumar SV. Clarification of the definition of complete response in multiple myeloma. Leukemia. 2015 Dec;29(12):2416-7. doi: 10.1038/leu.2015.290. Epub 2015 Oct 21. No abstract available.

  PMID: 26487274 BACKGROUND

• Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73. doi: 10.1038/sj.leu.2404284. Epub 2006 Jul 20.

  PMID: 16855634 BACKGROUND

• Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 - Myeloma Academy. (2017, November 27). https://academy.myeloma.org.uk/resources/common-terminology-criteria-for-adverse-events-ctcae-version-5-0

  BACKGROUND

• Buonato JM, Edwards JP, Zaritskaya L, Witter AR, Gupta A, LaFleur DW, Tice DA, Richman LK, Hilbert DM. Preclinical Efficacy of BCMA-Directed CAR T Cells Incorporating a Novel D Domain Antigen Recognition Domain. Mol Cancer Ther. 2022 Jul 5;21(7):1171-1183. doi: 10.1158/1535-7163.MCT-21-0552.

  PMID: 35737298 BACKGROUND

• Avery DT, Kalled SL, Ellyard JI, Ambrose C, Bixler SA, Thien M, Brink R, Mackay F, Hodgkin PD, Tangye SG. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J Clin Invest. 2003 Jul;112(2):286-97. doi: 10.1172/JCI18025.

  PMID: 12865416 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Maryam Khan, MBBS, MRCP (UK), FCPS(Cl Haem)

  National University of Medical Sciences

  STUDY CHAIR

• Tariq Ghafoor

  National University of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nadia Sial, Ph.D

CONTACT

+923315582265; nadiaharif@gmail.com

Maryam Khan, MBBS, MRCP(UK), FCPS (Cl Haem)

CONTACT

+923366395758

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Pilot, Open-Label, Single-Arm Study

Study Record Dates

• First Submitted: June 27, 2026
• First Posted: July 8, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: after 31st December 2027 till 31st December 2028
• Access Criteria: Access will be given by requesting PI by email

Locations

PA (2)