A phase I/II open label, multicenter study evaluating the feasibility, safety and efficacy of point-of-care manufactured anti-BCMA CAR T cells (BCMACP03) in subjects with relapsed/refractory Multiple Myeloma (r/r MM)
- Conditions
- relapsed/refractory Multiple MyelomaTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- CTIS2022-500782-27-00
- Lead Sponsor
- Galapagos
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 20
1.Signed informed consent form 2.Age = 18 years 3.Multiple myeloma diagnosis according to the IMWG diagnostic criteria 4.Relapsed or refractory disease (refractory defined as documented evidence of PD by IMWG criteria on or within 60 days of the last regimen), after at least 2 prior lines of therapy including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and anti-CD38 antibody treatment. -Subject must have undergone at least 1 complete cycle of treatment for each line of therapy, unless PD was the best response to the line of therapy or if patient was ineligible for any of these agents Note: Induction with or without autologous hematopoietic stem cell transplant (HSCT), consolidation and maintenance therapy is considered a single line of therapy 5.Measurable disease at screening as defined by any one or more of the following criteria: -Serum M-protein level = 0.5 g/dL -Urine M-protein level = 200 mg/24 hours -Serum free light chain level = 10 mg/dL and abnormal serum free light chain ratio 6.ECOG performance status of 0 - 2 (subjects with ECOG 2 must have serum albumin =3.4 g/dL) 7.Adequate bone marrow function defined as: -Hemoglobin = 8 g/dL or = 5 mmol/L (without prior RBC transfusion within 7 days before the laboratory test) -Absolute neutrophil count (ANC) = 1,000/µL or = 1.0 × 109/L (without G-CSF support within 7 days of the laboratory test or pegylated G-CSF support within 14 days of the laboratory test) -Thrombocyte count = 50,000/µL or = 50 × 109/L, without prior thrombocyte transfusion within 7 days before the laboratory test -Absolute lymphocyte count (ALC) = 300/µL or = 0.3 × 109/L -Absolute number of CD3+ T cells = 150/µL or = 0.15 × 109/L 8.Adequate renal, hepatic, cardiac, and pulmonary function defined as: -Creatinine clearance (Cockcroft Gault) = 45 mL/min -Aspartate aminotransferase (AST) = 3 × ULN -Alanine aminotransferase (ALT) = 3 × ULN -Total bilirubin = 2 x ULN, except in subjects with Gilbert’s syndrome -Normal cardiac function (LVEF = 45%) as assessed by MUGA or echocardiogram. In patients with symptoms of pericardial effusion this must be excluded by echocardiogram -Baseline oxygen saturation > 92% on room air 9.Women of childbearing potential must have a negative serum pregnancy test at screening and prior to the first dose of cyclophosphamide and fludarabine 10.Women of childbearing potential and all male subjects must agree to use highly effective methods of contraception (failure rate of < 1% per year when used consistently and correctly) and agree to remain on a highly effective method of contraception from the time of signing the informed consent form until at least 12 months after BCMACP03 infusion. Subjects must agree to not donate eggs or sperm during this period
1.AL Amyloidosis, Waldenström’s Macroglobulinemia, POEMS syndrome 2.Prior treatment (should be discontinued at time of screening, except for corticosteroid therapy): -BCMA-directed therapy -Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 14 days before leukapheresis or at least 5 half-lives, whichever is less. -Monoclonal antibody treatment within 21 days before leukapheresis -Cytotoxic therapy within 14 days before leukapheresis, alkylating agents within 6 weeks before leukapheresis -Proteasome inhibitor therapy within 14 days before leukapheresis -Immunomodulatory agent therapy within 7 days before leukapheresis -Radiotherapy within 14 days before leukapheresis. However, if the radiation portal covered =5% of the bone marrow reserve, the subject is eligible irrespective of the end date of radiotherapy. Radiotherapy within 14 days before leukapheresis on measurable extramedullary plasmacytoma(s) is not permitted even in the setting of palliation for symptomatic management. -Allogeneic HSCT within 6 months before leukapheresis. Subjects who received an allogeneic transplant must have stopped all immunosuppressive medications for 6 weeks without signs of GVHD. Subjects with active GVHD are excluded -Corticosteroid therapy at a pharmacologic dose (> 5 mg/day of prednisone or equivalent doses of other corticosteroids) and other immunosuppressive drugs are not allowed for 7 days prior to leukapheresis and > 72 hours prior to BCMACP03 infusion (if restarted) 3.History of another primary malignancy that requires intervention beyond surveillance or that has not been in remission for at least 3 years. The following are exempt from the 3-year limit -Non-melanoma skin cancer -Curatively treated localized prostate cancer -Cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear 4.Toxicity from previous anticancer therapy must recover to = Grade 2 (according to CTCAE v5.0) or subject’s baseline level except for peripheral neuropathy attributable to prior MM therapy 5.Clinically significant cardiac disease within 12 months of screening such as: -New York Heart Association Class III or IV congestive heart failure -Myocardial infarction or coronary-artery-bypass graft =6 months prior to screening -Clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration; -arrhythmias or unexplained syncope -History of severe non-ischemic cardiomyopathy 6.Infection with HIV-1/2, hepatitis B or hepatitis C virus. A history of hepatitis B or C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing 7.Uncontrolled infection at enrollment 8.Other medical contraindications: -Known active or prior history of CNS involvement or clinical signs of meningeal involvement of MM, except if the CNS involvement has been effectively treated (i.e. patient is asymptomatic) and local treatment was > 4 weeks before screening -Primary immunodeficiency -Stroke or seizure within 6 months of screening -History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within 2 years prior to screening -Contraindications to leukapheresis or inadequate venous access -Known allergy or hypersensitivity to tocilizumab 9.Vaccinated with live attenuated vaccine = 6 weeks
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method