A Phase I Trial to Establish the Safety and Maximum Tolerated Dose of High-affinity Autologous BCMA-targeting Chimeric Antigen Receptor (CAR) T-cells in Patients With Relapsed and Refractory B-cell Malignancies

NCT05836896 | Recruiting Phase 1

• 1 other identifier: TUD-BCMACA-078
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this phase I study is to determine whether MDC-CAR-BCMA001 (BCMA directed CAR T-cells) is safe and tolerable in the treatment of relapsed and refractory B-cell malignancies

Conditions

Neoplasms; Relapsed Diffuse Large B-cell Lymphoma (DLBCL); Refractory Diffuse Large B-cell Lymphoma (DLBCL); Multiple Myeloma, Refractory; Multiple Myeloma in Relapse

Outcome Measures

Primary Outcomes (5)

• Maximum tolerated dose (MTD) of MDC-CAR-BCMA001

  The MTD will be defined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate.

  appr. 24 months

• Incidence and severity of adverse events and serious adverse events

  graded according to Common Terminology Criteria of Adverse Events V5.0

  appr. 24 months

• Incidence and severity of Cytokine release syndrome

  Grading of Cytokine release syndrome according to American Society for Transplantation and Cellular Therapy consensus criteria

  appr. 24 months

• Incidence and severity of Immune effector cell-associated neurotoxicity syndrome

  Grading of Immune effector cell-associated neurotoxicity syndrome according to American Society for Transplantation and Cellular Therapy consensus criteria

  appr. 24 months

• Incidence of dose-limiting toxicity (DLT) during DLT-evaluation period and beyond

  appr.24 months

Study Arms (1)

MDC-CAR-BCMA001

EXPERIMENTAL

MDC-CAR-BCMA001 will be administered intravenously in ascending dose levels. This trial will test a total of 4 dose levels in order to identify the MTD and/or recommended phase 2 dose for MDC-CAR-BCMA001.

Genetic: MDC-CAR-BCMA001 (BCMA directed CAR T-cells)

Interventions

MDC-CAR-BCMA001 (BCMA directed CAR T-cells) GENETIC

Single-dose intravenous infusion of MDC-CAR-BCMA001 at the respective dose level following a conditioning chemotherapy

MDC-CAR-BCMA001

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged ≥ 18 years
• Written informed consent of the subject
• Able and willing to adhere to the trial protocol
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Either Multiple Myeloma (MM):
• relapsed or refractory disease after at least 2 lines of treatment including an Immunomodulatory drug, a proteasome inhibitor and an anti-cluster of differentiation 38 antibody or anti-cluster of differentiation 319 (SLAMF7; Elotuzumab) antibody AND
• not eligible for treatment with other regimen available according to local standard of care and known to confer clinical benefit according to the investigator's discretion, prior treatment with other BCMA-targeting immunotherapies (including T-cell engaging antibodies, CAR T-cells and antibody-drug immuno-conjugates) is allowed AND
• measurable disease defined by serum M-Protein ≥ 10 g/l OR urine M-Protein ≥ 200 mg/24h OR serum free light chain \> 100 mg/l of involved free light chain and abnormal serum free light chain ratio
• Diffuse large B-cell lymphoma (DLBCL):
• Relapsed after or refractory to standard curative therapy (such as R-CHOP) and refractory to at least one course of standard salvage chemotherapy OR
• Relapsed within one year after high-dose chemotherapy and autologous stem cell support OR
• Relapsed after allogeneic stem-cell transplantation or approved anti-cluster of differentiation 19 CAR T-cell therapies.
• AND (applicable to all DLBCL patients)
• Not be eligible for treatment with other regimen available according to local standard of care and known to confer clinical benefit. This includes but is not limited to anti-cluster of differentiation 19 directed CAR T-cell therapies with approved constructs AND (applicable to all DLBCL patients)
• Measurable disease according to Lugano criteria

You may not qualify if:

• Any Central nervous system (CNS)-involvement by underlying disease
• History of seizure or cerebrovascular ischemia / hemorrhage within the last 12 months
• History of any autoimmune Central nervous system disease (e.g. multiple sclerosis, amyotrophic lateral sclerosis, optic neuritis)
• Ongoing neurologic conditions that in the opinion of the investigator might increase the risk for neurotoxicity or impair the assessment of CAR-associated neurotoxicity
• Inadequate pulmonary function (i.e. need for continuous oxygen support)
• Patients on hemodialysis
• Any contraindications to Fludarabine and/or Cyclophosphamide as given in the Summary of product characteristics
• Any other active malignancy requiring active treatment or interfering with the assessment of primary or secondary trial endpoints, adjuvant hormonal therapy is allowed
• Positivity for anti-human immunodeficiency virus (HIV) immunoglobulin
• Active or chronic infectious hepatitis B (HBV) and C (HCV) virus unless serology demonstrates clearance of infection (i.e. Polymerase chain reaction undetectable viral load for hepatitis)
• Active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) or history of SARS-CoV2 infection within the past 3 months or active long coronavirus disease (COVID) syndrome
• Uncontrolled bacterial, viral or fungal infections defined as infections needing in-patient and/or i.v. antimicrobial treatment\*
• Active Graft versus Host Disease defined as active symptoms of graft-versus-host disease or ongoing immunosuppressive treatment or prophylaxis within the last 30 days prior to application of MDC-CAR-BCMA001
• Psychologic disorders, drug abuse or any other condition which might significantly impair a patient's ability to comply with the trial protocol
• Patients who are expected to deteriorate during the time needed for manufacturing MDC-CAR-BCMA001 in spite of bridging therapy in the opinion of the investigator including

Sponsors & Collaborators

• Technische Universität Dresden: lead
• German Cancer Research Center: collaborator

Study Sites (1)

Technische Universität Dresden, NCT/UCC, Early Clinical Trial Unit

Dresden, 01307, Germany

RECRUITING

MeSH Terms

Conditions

Neoplasms; Lymphoma, Large B-Cell, Diffuse; Multiple Myeloma

Condition Hierarchy (Ancestors)

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

Study Officials

• Martin Wermke, Prof.

  Technische Universität Dresden (TUD)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Wermke, Prof.

CONTACT

+49 351 458 13408; carlotta@ukdd.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2023
• First Posted: May 1, 2023
• Study Start: February 15, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: August 24, 2025

Record last verified: 2025-08

Locations

DE (1)