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

A vizsgálat adatai

Ki végzi

Technische Universität Dresden

Azonosító

NCT05836896EU 2022-502831-20-00

A regiszteradat frissítve

2026. augusztus 27.

Eredeti leírás

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 malignanciesA teljes eredeti leírásKevesebb

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

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

Bevonási feltételek: 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; OR; 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; Adequate organ function defined as:; Neutrophils ≥ 0.5 Gpt/l and Platelets ≥ 50 Gpt/l (unless due to subtotal infiltration of the bone marrow by underlying malignancy); Lymphocytes ≥ 0.1 Gpt/l; Alaninaminotransferase and Asparataminotransferase ≤ 3.0x Upper limit of normal; Bilirubin ≤ 1.5x Upper limit of normal; Creatinine ≤ 1.5x Upper limit of normal; Adequate cardiac function i.e. left ventricular ejection fraction ≥ 50%, no major valve abnormalities or dyskinesias; A female of childbearing potential* may be enrolled providing she has a negative pregnancy test at screening and is routinely using a highly effective method of birth control (pearl index of ≤ 1 required) resulting in a low failure rate (e.g. hormonal contraception, intrauterine device, total sexual abstinence or sterilization). Male patients must also prac-tice a highly effective method of birth control and should not father a child at least until 12 months after infusion of CAR T-cells.

Kizáró feltételek: 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; 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; Any condition requiring systemic treatment with immunosuppressive drugs (including but not limited to steroids exceeding 20 mg Prednisolone per day); Any antineoplastic treatment within 7 days prior to leukapheresis or within 2 weeks or 5 half-lives (whatever is shorter) of the start of lymphodepleting chemotherapy (palliative radiotherapy to lesions not essential for response assessment is allowed without a minimal washout period); Any investigational therapy within 4 weeks or 5 half-lives (whatever is shorter) prior to apheresis or the start of lymphodepleting chemotherapy; Receipt of live vaccines within 2 weeks prior to leukapheresis and start of lymphodepleting chemotherapy; Simultaneous participation in another interventional clinical trial (including within the last 4 weeks before inclusion); 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; 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 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*; Psychologic disorders, drug abuse or any other condition which might significantly impair a patient's ability to comply with the trial protocol; History of allergic reactions to any drug or its ingredients / impurities foreseen to be given as part of this trial according to the protocol*; Hypersensitivity known from medical history to one of the drugs used or their ingredients or to drugs with a similar chemical structure; Addictions or other illnesses that do not allow the person concerned to assess the nature and extent of the clinical trial and its possible consequences; 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); Women of childbearing potential, except women who meet the following criteria:; post-menopausal (12 months natural amenorrhoea or 6 months amenorrhoea with serum Follicle stimulating hormone > 40 U/ml); postoperative (6 weeks after bilateral ovariectomy with or without hysterectomy); regular and correct use of a contraceptive method with an Pearl Index < 1% per year; sexual abstinence; Vasectomy of the partner; 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; Pregnant or breastfeeding women. Breastfeeding has to be discontinued before onset of and during treatment and should be discontinued for at least 3 months after end of treatment; Indications that the subject is unlikely to adhere to the protocol (e.g., lack of compliance).

ClinicalTrials.gov NCT05836896 · EU CTIS 2022-502831-20-00