A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients With AL Amyloidosis (AFFIRM-AL)
Light Chain (AL) Amyloidosis
About this trial
This is an interventional treatment trial for Light Chain (AL) Amyloidosis focused on measuring Light Chain (AL) Amyloidosis, Mayo Stage IV, birtamimab
Eligibility Criteria
Key Inclusion Criteria:
- Aged ≥18 years and legal age of consent according to local regulations
- Newly diagnosed and AL amyloidosis treatment-naïve with cardiac involvement
- Confirmed diagnosis of AL amyloidosis
- Confirmed Mayo Stage IV AL Amyloidosis as defined by NT-proBNP ≥1800 pg/mL and Troponin-T >0.03 ng/mL and dFLC ≥18 mg/dL
- Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly.
Key Exclusion Criteria:
- Non-AL amyloidosis.
- NT-proBNP >8500 pg/mL.
- Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma
- Subject is eligible for and plans to undergo ASCT or organ transplant during the study.
- Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit.
- Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease.
- ECG evidence of acute ischemia or active conduction system abnormalities
- Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1.
- Prior radiotherapy within 4 weeks of Month 1-Day 1.
- Prior treatment with plasma cell-directed chemotherapy, birtamimab, daratumumab, 11- 1F4, anti-serum amyloid P antibody, doxycycline for amyloid, or other investigational treatment directed at amyloid .
- Waldenström's macroglobulinemia and/or immunoglobulin M monoclonal gammopathy
Sites / Locations
- St. Francis HospitalRecruiting
- Yale Cancer CenterRecruiting
- Smilow Cancer Hospital Care Center at TrumbullRecruiting
- MedStar Georgetown University HospitalRecruiting
- Cleveland Clinic FloridaRecruiting
- Johns Hopkins UniversityRecruiting
- Boston University School of Med.Recruiting
- Dana-Farber Cancer InstituteRecruiting
- University of Michigan Rogel Cancer CenterRecruiting
- Barbara Ann Karmanos Cancer InstituteRecruiting
- Mayo Clinic - RochesterRecruiting
- University of Nebraska Medical CenterRecruiting
- Hackensack University Medical CenterRecruiting
- Roswell Park Comprehensive Cancer CenterRecruiting
- Perlmutter Cancer Center - 38th StreetRecruiting
- New York University Langone Hospital - Long Island
- Duke Clinical Research InstituteRecruiting
- Wake Forest Baptist Health - Comprehensive Cancer CenterRecruiting
- Cleveland Clinic Main CampusRecruiting
- The Ohio State University College of MedicineRecruiting
- University of Tennessee Medical CenterRecruiting
- Baylor University Medical CenterRecruiting
- University of WashingtonRecruiting
- Froedtert and Medical College of WisconsinRecruiting
- SESLHD: St George HospitalRecruiting
- Icon Cancer Centre - WesleyRecruiting
- Icon Cancer CenterRecruiting
- Royal Adelaide HospitalRecruiting
- Box Hill Hospital
- Royal Perth HospitalRecruiting
- Paracelsus Medical UniversityRecruiting
- Medizinische UniversitätRecruiting
- Medizinische Universität WienRecruiting
- AZ Sint-Jan Brugge-Oostende AVRecruiting
- CHU UCL Namur (Site Godinne)Recruiting
- Tom Baker Cancer CentreRecruiting
- Royal Victoria HospitalRecruiting
- Fakultní Nemocnice BrnoRecruiting
- Fakultni nemocnice ostravaRecruiting
- Všeobecná fakultní nemocnice v PrazeRecruiting
- Odense UniversitetshospitalRecruiting
- Hôpital BretonneauRecruiting
- Hôpital Haut-LévêqueRecruiting
- Hopital NeckerRecruiting
- Pitie-Salpêtrière HospitalRecruiting
- Hôpitaux de BraboisRecruiting
- Hopital RangueilRecruiting
- Hôpital Claude HuriezRecruiting
- CHU NantesRecruiting
- Centre Hospitalier Universitaire PoitiersRecruiting
- CHU de BordeauxRecruiting
- Hopital Henri Mondor, CreteilRecruiting
- Centre Hospitalier Universitaire LimogesRecruiting
- Hôpital Necker-Enfants MaladesRecruiting
- Universitätsklinikum HeidelbergRecruiting
- Uniklinik KölnRecruiting
- University Medicine MainzRecruiting
- Charité Campus Mitte
- Alexandra General HospitalRecruiting
- Theagenio Anti-Cancer Hospital of ThessalonikiRecruiting
- University Hospital of PatrasRecruiting
- Pécsi Tudományegyetem Klinikai Központ
- Szent-Györgyi Albert Klinikai KözpontRecruiting
- Debreceni Egyetem Klinikai KözpontRecruiting
- Semmelweis Egyetem - I. sz. Belgyógyászati Klinika
- Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai IntézetRecruiting
- Cork University Hospital
- Cancer Clinical Trials and Research Unit, Beaumont HospitalRecruiting
- Bnai Zion Medical CenterRecruiting
- Rambam Medical CenterRecruiting
- Hadassah Medical CenterRecruiting
- Rabin Medical Center - Beilinson HospitalRecruiting
- Samson Assuta Ashdod HospitalRecruiting
- Barzilai Medical CenterRecruiting
- Carmel Medical CenterRecruiting
- Azienda Ospedaliero Universitaria Ospedali Riuniti Di AnconaRecruiting
- Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-MalpighiRecruiting
- ASST Spedali CiviliRecruiting
- Azienda Ospedaliero Universitaria Policlinico Gaspare Rodolico - San MarcoRecruiting
- Fondazione IRCCS Policlinico San MatteoRecruiting
- Azienda Ospedaliero-Universitaria PisanaRecruiting
- Umberto I - Policlinico di RomaRecruiting
- Kyoto Kuramaguchi Medical CenterRecruiting
- Shinshu University HospitalRecruiting
- Jichi medical university hospitalRecruiting
- Tokushima University HospitalRecruiting
- Red Cross Medical CenterRecruiting
- Nagoya City University HospitalRecruiting
- Fukushima Medical University HospitalRecruiting
- Keimyung University Dongsan HospitalRecruiting
- Chonnam National University Hwasun HospitalRecruiting
- Severance HospitalRecruiting
- Pusan National University HospitalRecruiting
- Kosin University Gospel HospitalRecruiting
- Gachon University Gil Medical CenterRecruiting
- Seoul National University HospitalRecruiting
- Hanyang University Seoul HospitalRecruiting
- Samsung Medical CenterRecruiting
- The Catholic University of Korea - Seoul St. Mary's HospitalRecruiting
- Maastricht Universitair Medisch CentrumRecruiting
- Universitair Medisch Centrum Groningen
- Klinika Hematologii i TransplantologiiRecruiting
- Hospital de BragaRecruiting
- Centro Hospitalar e Universitário de CoimbraRecruiting
- Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa MariaRecruiting
- Hospital Universitario Son EspasesRecruiting
- Hospital Son LlatzerRecruiting
- Institut Català d'Oncologia - Hospital Germans Trias i PujolRecruiting
- University Hospital Marqués de ValdecillaRecruiting
- Hospital Universitario Puerta de Hierro - MajadahondaRecruiting
- Clinica Universidad de Navarra -MadridRecruiting
- Clinica Universidad de Navarra - PamplonaRecruiting
- Hospital Universitario de CanariasRecruiting
- Hospital Universitari Vall d'hebronRecruiting
- Hospital Clinic of BarcelonaRecruiting
- Institut Català d'Oncologia - Hospital Duran i ReynalsRecruiting
- Hospital Josep Trueta ICO GironaRecruiting
- Hospital Ramon y CajalRecruiting
- Complejo Asistencial Universitario de Salamanca - Hospital ClínicoRecruiting
- Hospital Universitari i Politècnic la FeRecruiting
- Hospital Universitario 12 de OctubreRecruiting
- National Taiwan University HospitalRecruiting
- Kaohsiung Chang Gung Memorial HospitalRecruiting
- Taipei Veterans General HospitalRecruiting
- Ankara UMFRecruiting
- Gazi UniversityRecruiting
- Istanbul University Cerrahpasa Medical Faculty
- Ege Universitesi Tip FakultesiRecruiting
- University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth HospitalRecruiting
- The Newcastle Upon Tyne Hospitals NHS Foundation TrustRecruiting
- Barts Health NHS TrustRecruiting
- Univiersity College London HospitalsRecruiting
- Manchester University NHS Foundation Trust
- Nottingham University Hospitals NHS Trust
- Belfast City Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Birtamimab plus Standard of Care Chemotherapy
Placebo plus Standard of Care Chemotherapy
Intravenous administration of 24 mg/kg birtamimab every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD) according to the institutional standard of care. Initiation of daratumumab at randomization allowed at the discretion of the investigator
Intravenous 0.9% Saline administration as a placebo every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD) according to the institutional standard of care. Initiation of daratumumab at randomization allowed at the discretion of the investigator