A Study to Evaluate Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease

Официальное название

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease (AXemplify-357)

Обзор

This study will be conducted to compare the efficacy of axatilimab versus placebo in combination with corticosteroids as initial treatment for moderate or severe chronic graft-versus-host disease (cGVHD).

Вмешательства

• Препарат INCA034176
  IV infusion
• Препарат Placebo
  IV infusion
• Препарат Corticosteroids
  Oral/IV Infusion

Первичные конечные точки

• Event Free Survival (EFS) [Срок оценки: Up to 3 years]

Вторичные конечные точки (12)

• Objective Response (OR) [Срок оценки: 6 months]
• Event Free Survival 2 [Срок оценки: Up to 3 years]
• Proportion of participants with a ≥ 7-point improvement in mLSS total score [Срок оценки: Up to 3 years]
• Overall Response [Срок оценки: 12 Months]
• DOR (in responders only) [Срок оценки: Up to 3 years]
• Best Overall Response (BOR) [Срок оценки: Up to 3 years]
• Overall Survival (OS) [Срок оценки: Up to 3 years]
• Nonrelapse mortality (NRM) [Срок оценки: Up to 3 years]
• Failure-free survival (FFS) [Срок оценки: Up to 3 years]
• Relapse of hematologic diseases [Срок оценки: Up to 3 years]
• Time to primary hematologic disease relapse [Срок оценки: Up to 3 years]
• Percent reduction in daily corticosteroid dose [Срок оценки: 6 months]

Критерии участия

Критерии включения

• ≥ 12 years of age at the time of informed consent.
• New-onset moderate or severe cGVHD, as defined by the 2014 NIH Consensus Development Project Criteria for Clinical Trials in cGVHD, requiring systemic therapy.
• 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.
• Adequate hematologic function with ANC ≥ 0.5 × 109/L independent of growth factors for at least 7 days prior to study entry.
• Willingness to avoid pregnancy or fathering children.

Критерии исключения

• Received more than 1 prior allo-HCT. Prior autologous HCT is allowed.
• Has overlap cGVHD, defined as simultaneous presence of features or characteristics of aGVHD in a patient with cGVHD.
• Received more than 7 days of systemic corticosteroid treatment for cGVHD or unable to begin a prednisone dose ≥ 1.0 mg/kg per day (or methylprednisolone equivalent) for cGVHD.
• Received previous systemic treatment for cGVHD, including extracorporeal photopheresis.
• Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.
• Prior treatment with CSF-1R targeted therapies.
• Active, uncontrolled bacterial, fungal, parasitic, or viral infection.
• Evidence of relapse of the primary hematologic disease or treatment for relapse after the allo-HCT was performed, including DLIs for the treatment of molecular relapse.
• History of acute or chronic pancreatitis.
• Active symptomatic myositis.
• History or current diagnosis of cardiac disease indicating significant risk of safety for participation in the study, such as uncontrolled or significant cardiac disease.
• Severe renal impairment, that is, estimated CrCl < 30 mL/min measured or calculated by Cockcroft-Gault equation in adults and Schwartz formula in pediatric participants, or endstage 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.
• 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

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 36 центров

• University of Alabama Birmingham — Birmingham
• University of Arizona Cancer Center-Out Pt. — Tucson
• City of Hope Medical Center — Duarte
• University of California San Diego Medical Center, Moores Cancer Center — La Jolla
• University of Southern California — Los Angeles
• UCSF — San Francisco
• Colorado Blood Cancer Institute — Denver
• Childrens National Hospital — Washington D.C.
• … и ещё 28 центров

Италия · 17 центров

• Azienda Ospedaliero-Universitaria Di Alessandria Ss.Antonio E Biagio E Cesare Arrigo — Alessandria
• Azienda Ospedaliero Universitaria Delle Marche — Ancona
• Aou Policlinico Consorziale Di Bari — Bari
• … и ещё 14 центров

Германия · 14 центров

• University Medical Center Rwth Aachen — Aachen
• Charite Universitatsmedizin Berlin — Berlin
• Universitaetsklinikum Bonn, University Hospital Bonn — Bonn
• University Clinic Carl Gustav Carus Technical University Dresden — Dresden
• University Hospital Duesseldorf — Düsseldorf
• Universitaetsklinikum Erlangen — Erlangen
• Universitatsklinikum Essen — Essen
• Universitatsklinikum Halle (Saale) — Halle
• … и ещё 6 центров

Япония · 13 центров

Список центров уточняется — проверьте первичный протокол.

Испания · 10 центров

Список центров уточняется — проверьте первичный протокол.

Франция · 9 центров

• Chu Amiens Picardie - Hopital Sud — Amiens
• Institut Paoli Calmettes — Marseille
• Hopitaux de Brabois — Nancy
• Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu — Nantes
• Chu de Nice - Hospital L Archet — Nice
• Hospital Saint Louis — Paris
• Hospital Saint Antoine — Paris
• Hospices Civils de Lyon Centre Hospitalier Lyon Sud — Pierre-Bénite
• … и ещё 1 центр

Канада · 8 центров

• Alberta'S Children Hospital — Calgary
• Stollery Children'S Hospital — Edmonton
• Bc Children'S Hospital — Vancouver
• Queen Elizabeth Ii Health Sciences Centre — Halifax
• Juravinski Cancer Centre — Hamilton
• Princess Margaret Cancer Center — Toronto
• Hospital Maisonneuve Rosemont — Montreal
• Vancouver General Hospital — Vancouver

Великобритания · 7 центров

Список центров уточняется — проверьте первичный протокол.

Австрия · 5 центров

• Landeskrankenhaus Universitatsklinikum Graz — Graz
• Innsbruck University Hospital — Innsbruck
• Ordensklinikum Linz Gmbh Elisabethinen — LINZ CET
• Akh Und Medizinische Universitat Wien Universitatsklinik Fur Innere Medizin I — Vienna
• St. Anna Childrens Hospital — Vienna

Австралия · 3 центра

• Royal Prince Alfred Hospital — Sydney
• Royal Adelaide Hospital — Adelaide
• Austin Health Medical Oncology and Clinical Haematology — Heidelberg

Нидерланды · 2 центра

Список центров уточняется — проверьте первичный протокол.

Дания · 1 центр

• Rigshospitalet — Copenhagen

Ирландия · 1 центр

• St. James Hospital — Dublin

Идентификаторы

NCT: NCT06585774 · INCA34176-357 · 2023-510292-65-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗