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)

Official title

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)

Overview

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.

Interventions

• Drug INCA034176
  Axatilimab at the protocol-defined dose.
• Drug 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.

Primary outcome measures

• Objective Response (OR) at 6 months [Time frame: 6 months]

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• 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
• … and 3 more centers

United Kingdom · 9 centers

• 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
• … and 1 more center

Spain · 7 centers

• 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

Germany · 6 centers

• 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

Italy · 6 centers

• 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

Belgium · 2 centers

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

Identifiers

NCT: NCT07124078 · INCA034176-256

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗