Onderzoek naar de werkzaamheid en veiligheid van Ruxolitinib bij patiënten met graad II tot IV steroïde-refractaire acute graft versus host-ziekte
Een eenarmige, multicentrische studie van Ruxolitinib voor de behandeling van Chinese patiënten met corticosteroïden-refractaire acute graft-versus-hostziekte graad II-IV
The purpose of this study is to assess the efficacy and safety of ruxolitinib therapy in Chinese adults and adolescents (≥ 12 years old) with Grade II-IV steroid-refractory acute graft versus host disease (SR-aGvHD).
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
Participants will start with a screening period to assess the eligibility; only participants who meet all the inclusion and none of the exclusion criteria will start study treatment from Day 1 to Week 24 or end of treatment. Following safety follow up visits, participants will receive the long-term follow-up until Month 12.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 4
Contacten en locaties
Studie Locaties
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Beijing, China, 100034
- Novartis Investigative Site
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Beijing, China, 100070
- Novartis Investigative Site
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Taian, China, 271000
- Novartis Investigative Site
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Tianjin, China, 300020
- Novartis Investigative Site
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Guangdong
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Guangzhou, Guangdong, China, 510515
- Novartis Investigative Site
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Henan
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Zhengzhou, Henan, China, 450003
- Novartis Investigative Site
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Hubei
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Wuhan, Hubei, China, 430030
- Novartis Investigative Site
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Shanxi
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Xian, Shanxi, China, 710061
- Novartis Investigative Site
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Zhejiang
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Hangzhou, Zhejiang, China, 310003
- Novartis Investigative Site
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Key Inclusion criteria
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Male or female Chinese participants aged 12 or older at the time of informed consent. Written informed consent from participant, parent or legal guardian.
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Able to swallow tablets.
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Have undergone alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood.
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Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive therapy.
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Evident myeloid and platelet engraftment (confirmed within 48 hours prior to study treatment (ruxolitinib) start):
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Confirmed diagnosis of steroid refractory aGvHD defined as participants administered systemic corticosteroids (methylprednisolone at least 1 mg/kg/day [or equivalent prednisone dose at least 1.25 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either:
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Progression based on organ assessment after at least 3 days compared to organ stage at the time of initiation of systemic corticosteroid +/- CNI for the treatment of Grade II to IV aGvHD. OR
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Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of systemic corticosteroid +/-CNI for the treatment of Grade II to IV. OR
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Participants who fail corticosteroid taper defined as fulfilling either one of the following criteria:
- Requirement for an increase in the corticosteroid dose to methylprednisolone ≥ 1 mg/kg/day (or equivalent prednisone dose ≥ 1.25 mg/kg/day). OR
- Failure to taper the methylprednisolone dose to < 0.5 mg/kg/day (or equivalent prednisone dose <0.6 mg/kg/day) for a minimum of 7 days.
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Key Exclusion criteria
- Has received more than one systemic treatment for steroid refractory aGvHD. Participants who received JAK inhibitor therapy for any indication after initiation of current alloSCT conditioning.
- Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome with both acute and chronic GvHD features.
- Failed prior alloSCT within the past 6 months. Presence of relapsed primary malignancy after the alloSCT was performed.
- Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
- SR-aGvHD occurring after non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Note: Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
- Presence of significant respiratory disease, severely impaired renal function, clinically significant or uncontrolled cardiac disease, unresolved cholestatic and liver disorders (not attributable to aGvHD). Disorders and/or current therapy with medications that interfere with coagulation or platelet function.
Other protocol-defined inclusion / exclusion criteria may apply
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Ruxolitinib
Participants will receive ruxolitinib orally of 10 mg BID daily (given as two 5-mg tablets, approximately 12 hours apart). |
Ruxolitinib is taken orally daily at 10 mg BID, given as two 5-mg tablets.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Overall Response Rate (ORR) at Day 28 per Investigators
Tijdsspanne: Day 28
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The ORR at Day 28 defined as the percentage of participants demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, mixed response or nonresponse, according to standard criteria and assessed by investigators. |
Day 28
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Durable Overall response rate (ORR) at Day 56
Tijdsspanne: Day 56
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Durable ORR at Day 56 is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) at Day 28 and maintain a CR or PR at Day 56. |
Day 56
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Duration of Response (DOR)
Tijdsspanne: From Week 1 to long term follow up Month 12
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DOR is defined as the time from first response until aGvHD progression or the date of additional systemic therapies for aGvHD. |
From Week 1 to long term follow up Month 12
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Best overall response (BOR)
Tijdsspanne: From week 1 to Day 28
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Percentage of participants who achieved overall response (complete response (CR) + Partial response (PR) at any time point up to and including Day 28 and before the start of additional systemic therapy for aGvHD. |
From week 1 to Day 28
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Overall survival (OS)
Tijdsspanne: From the date of start of study treatment to date of death, up to approx. 12 months
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Overall survival (OS) is defined as the time from the date of start of study treatment to date of death due to any cause. |
From the date of start of study treatment to date of death, up to approx. 12 months
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Non-relapse mortality (NRM)
Tijdsspanne: From date of start of study treatment to date of death, up to approx. 12 months
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Non-relapse mortality (NRM) is defined as the time from date of start of study treatment to date of death not preceded by hematologic disease relapse/progression. |
From date of start of study treatment to date of death, up to approx. 12 months
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Event-free survival (EFS)
Tijdsspanne: From the date of start of study treatment to the date of hematologic disease relapse/progression, graft failure, or death, up to approx. 12 months
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Event-free survival (EFS) is defined as the time from the date of start of study treatment to the date of hematologic disease relapse/progression, graft failure, or death due to any cause. |
From the date of start of study treatment to the date of hematologic disease relapse/progression, graft failure, or death, up to approx. 12 months
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Failure-free survival (FFS)
Tijdsspanne: From the date of start of study treatment to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment, up to approx. 12 months
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Failure-free survival (FFS) is defined as the time from the date of start of study treatment to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment. |
From the date of start of study treatment to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment, up to approx. 12 months
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Malignancy Relapse/Progression (MR)
Tijdsspanne: From date of start of study treatment to hematologic malignancy relapse/progression, up to approx. 12 months
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Malignancy Relapse/Progression (MR) is defined as the time from date of start of study treatment to hematologic malignancy relapse/progression. Calculated for participants with underlying hematologic malignant disease. |
From date of start of study treatment to hematologic malignancy relapse/progression, up to approx. 12 months
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Reduction of daily corticosteroids dose
Tijdsspanne: Up to Day 56
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This includes the assessment of systemic corticosteroid use and daily dose, and the percentage of participants successfully tapered off all systemic corticosteroids until Day 56, by time intervals and overall. |
Up to Day 56
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Cumulative incidence of chronic GvHD
Tijdsspanne: From Week 1 to long term follow up of month 12
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Cumulative incidence of chronic GvHD (cGvHD) includes mild, moderate and severe occurrences. |
From Week 1 to long term follow up of month 12
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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie directeur: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- CINC424C2416
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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