A Study to Evaluate Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft-Versus-Host Disease After at Least 2 Prior Lines of Systemic Therapy (AGAVE-256)

Официальное название

A Phase 2, Randomized, Open-Label Study of Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft-Versus-Host Disease After at Least 2 Prior Lines of Systemic Therapy (AGAVE-256)

Обзор

This study will be conducted to compare Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy.

Вмешательства

• Препарат INCA034176
  Axatilimab at the protocol-defined dose.
• Препарат Best available Treatment (BAT)
  Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements.

Первичные конечные точки

• Objective Response (OR) at 6 months [Срок оценки: 6 months]

Вторичные конечные точки (12)

• Pharmacokinetics Parameter (PK): Cmax of axatilimab [Срок оценки: Up to 5 years]
• Pharmacokinetics Parameter: Tmax of axatilimab [Срок оценки: Up to 5 years]
• Pharmacokinetics Parameter: Cmin of axatilimab [Срок оценки: Up to 5 years]
• Pharmacokinetics Parameter: AUC(0-t) of axatilimab [Срок оценки: Up to 5 years]
• Pharmacokinetics Parameter: AUC 0-∞ of axatilimab [Срок оценки: Up to 5 years]
• Pharmacokinetics Parameter: CL of axatilimab [Срок оценки: Up to 5 years]
• Pharmacokinetics Parameter: Vz of axatilimab [Срок оценки: Up to 5 years]
• Pharmacokinetics Parameter: t1/2 of axatilimab [Срок оценки: Up to 5 years]
• Best Overall Response (BOR) [Срок оценки: Up to 5 years]
• Overall Response at 12 months [Срок оценки: 12 months]
• Duration of Response (DOR) (in responders only) [Срок оценки: Up to 5 years]
• Organ-specific response [Срок оценки: Up to 5 years]

Критерии участия

Критерии включения

• Aged ≥ 2 to < 18 years at the time of signing the informed consent.
• Active, moderate to severe cGVHD, requiring systemic immune suppression.
• Participants with refractory or recurrent cGVHD who have received at least 2 lines of systemic therapy, including corticosteroids and ruxolitinib.
• Concomitant use of systemic corticosteroids is allowed. Participants on systemic corticosteroids must be on a stable dose of corticosteroids for at least 2 weeks prior to C1D1. Topical and inhaled corticosteroid agents are allowed.
• Participants must accept to be treated with one of the following BAT options on C1D1: CNI (cyclosporine or tacrolimus), ECP, MMF, an mTOR inhibitor (everolimus or sirolimus), rituximab, imatinib, methotrexate, or ibrutinib.
• History of allo-HCT from any donor HLA type (related or unrelated donor with any degree of HLA matching) using any graft source (bone marrow, peripheral blood stem cells, or cord blood). Recipients of myeloablative, nonmyeloablative, or reduced-intensity conditioning are eligible.

Критерии исключения

• Receipt of more than 1 prior allo-HCT. Prior autologous HCT is allowed.
• Evidence of relapse of hematologic disease or treatment for relapse after the allo-SCT was performed, including DLI for the treatment of molecular relapse. Note: Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
• Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.
• Severe renal impairment, that is, GFR < 30 mL/min/1.73 m2 as estimated using modified Schwartz formula, or end-stage renal disease on dialysis.
• Impaired liver function, defined as total bilirubin > 1.5 × ULN and/or ALT and AST > 3 × ULN in participants with no evidence of liver cGVHD.
• History of acute or chronic pancreatitis.
• Active, symptomatic myositis.
• Female adolescent participants who are pregnant or breastfeeding.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 11 центров

• City of Hope Medical Center — Duarte
• Children'S Hospital Los Angeles Specialt — Los Angeles
• Lucile Packard Child Hospital End — Palo Alto
• Childrens National Medical Center — Washington D.C.
• Adventhealth Pediatric Cellular Therapy and Blood and Marrow Transplant — Orlando
• Childrens Healthcare of Atlanta — Atlanta
• Memorial Sloan Kettering Cancer Center — New York
• Levine Cancer Institute — Charlotte
• … и ещё 3 центра

Великобритания · 9 центров

• Birmingham Children'S Hospital - Birmingham Women'S and Children'S Nhs Foundation Trust — Birmingham
• Addenbrooke'S Hospital - Cambridge University Hospitals Nhs Foundation Trust — Cambridge
• The Royal Hospital For Children - Glasgow Health Board — Glasgow
• Leeds Childrens Hospital — Leeds
• St Mary'S Hospital, Paddington - Imperial College Healthcare Nhs Trust — London
• Great Ormond Street Hospital Nhs Trust — London
• Royal Manchester Children'S Hospital - Manchester University Nhs Foundation Trust — Manchester
• Royal Victoria Infirmary - the Newcastle Upon Tyne Hospitals Nhs Foundation Trust — Newcastle
• … и ещё 1 центр

Испания · 7 центров

• Hospital Universitario Vall D'Hebron — Barcelona
• Hospital Sant Joan de Deu Barcelona - Children'S Hospital — Esplugues de Llobregat
• Hospital Infantil Unversitario Nino Jesus — Madrid
• Hospital Universitario La Paz — Madrid
• Hospital Regional Universitario de Malaga- Hospital Materno Infantil — Málaga
• Hospital Universitario Virgen de La Arrixaca — Murcia
• Universitat de Valencia - Hospital Universitari I Politecnic La Fe de Valencia (Hospital L — Valencia

Германия · 6 центров

• Charite Campus Virchow — Berlin
• Klinikum Der Johann Wolfgang Goethe-Universitaet — Frankfurt am Main
• Universitaetsklinikum Freiburg Zentrum Fuer Kinderheilkunde- Und Jugendmedizin Klinik Iv: — Freiburg im Breisgau
• Universitaetsklinikum Hamburg-Eppendorf — Hamburg
• Medizinische Hochschule Hannover (Mhh) - Zentrum Fuer Kinderheilkunde Und Jugendmedizin - — Hanover
• University Hospital Regensburg — Regensburg

Италия · 6 центров

• Irccs - Aou Di Bologna - Sant'Orsola Malpighi — Bologna
• Irccs Istituto G. Gaslini, Universita Di Genova — Genova
• Fondazione Irccs San Gerardo Dei Tintori — Monza
• Azienda Ospedaliera Universitaria Di Padova — Padua
• Fondazione Irccs Policlinico San Matteo Di Pavia Oncoematologia Pediatrica, Universita Di — Pavia
• Irccs Ospedale Pediatrico Bambino Gesu — Rome

Бельгия · 2 центра

• Hôpital Universitaire Des Enfants Reine Fabiola — Brussels
• Universite Catholique de Louvain (Ucl) - Cliniques Universitaires Saint-Luc — Woluwe-Saint-Lambert

Идентификаторы

NCT: NCT07124078 · INCA034176-256

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗