Ruxolitinib for corticosteroid-refractory chronic graft-versus-host disease in Chinese patients

A Single-arm Multi-center Study of Ruxolitinib in Chinese Participants With Corticosteroid-refractory Chronic Graft Versus Host Disease After Allogeneic Stem Cell Transplantation

This trial will try ruxolitinib in Chinese adolescents (12+) and adults whose chronic graft-versus-host disease has not improved with corticosteroids.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 12 Years to 100 Years
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Drugs / interventions: prednisone, ruxolitinib
• Locations: 19 sites (Hefei, Anhui and 18 other locations)
• Trial ID: NCT06824103 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label, multi-center Phase 4 trial enrolling about 50 Chinese participants aged 12 years and older with moderate-to-severe corticosteroid-refractory chronic graft-versus-host disease after allogeneic stem cell transplant. Participants will receive oral ruxolitinib with treatment cycles of 28 days and will be followed on study for up to 164 weeks including safety and long-term survival follow-up. The trial requires baseline neutrophil and platelet thresholds and allows growth factor or transfusion support during treatment but not to meet screening limits. Outcomes collected include measures of cGvHD response, safety, and long-term survival.

Who should consider this trial

Good fit: Ideal candidates are Chinese males or females aged 12 or older with moderate-to-severe corticosteroid-refractory chronic GvHD after alloSCT who meet minimum neutrophil and platelet counts and can take oral tablets.

Not a fit: Patients with mild cGvHD, those who cannot meet the blood-count entry requirements, cannot swallow tablets, or who have conditions that exclude ruxolitinib use are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, ruxolitinib could reduce cGvHD symptoms and steroid dependence for Chinese patients with corticosteroid-refractory disease.

How similar studies have performed: Previous larger trials, including randomized phase 3 studies, have shown ruxolitinib can improve outcomes in corticosteroid-refractory cGvHD, so this study is largely confirming efficacy and safety in a Chinese population.

Eligibility criteria

Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study.
* Male or female Chinese participants aged 12 or older at the time of informed consent
* Able to swallow tablets.- Have undergone alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible.
* Evident myeloid and platelet engraftment:

  * Absolute neutrophil count (ANC) \>1,000/mm3 AND
  * Platelet count ≥25,000/mm3

Note: Use of growth factor supplementation and transfusion support is allowed during the trial, however, transfusion to reach a minimum platelet count for inclusion is not allowed during screening and at baseline.

* Participants with clinically diagnosed cGvHD staging of moderate to severe according to NIH Consensus Criteria (Jagasia et al 2015) prior to Cycle 1 Day 1.

  * Moderate cGvHD: at least one organ (not lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1.
  * Severe cGvHD: at least 1 organ with a score of 3, or lung score of 2 or 3.
* Participants currently receiving systemic corticosteroids for the treatment of cGvHD for a duration of \< 12 months prior to Cycle 1 Day 1, and have a confirmed diagnosis of corticosteroid refractory cGvHD defined per 2014 NIH consensus criteria (Martin et al 2015) irrespective of the concomitant use of a calcineurin inhibitor, as follows:

  * A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week (or equivalent) OR
  * Disease persistence without improvement despite continued treatment with prednisone at \>0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks (or equivalent) OR
  * Increase to prednisone dose to \>0.25 mg/kg/day after two unsuccessful attempts to taper the dose (or equivalent)
* Participants has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

For a full list of exclusion criteria, refer to Section 5.2. Key exclusion criteria include

* Participants who have received two or more systemic treatments for cGvHD in addition to corticosteroids ± CNI for cGvHD.
* Participants who have received ROCK2 inhibitors for cGvHD.
* Participants that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment

Note: Participants receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed.

* Participants who were treated with prior JAK inhibitors for aGvHD; except when the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks prior to Cycle 1 Day 1.
* Failed prior alloSCT within the past 6 months from Cycle 1 Day 1.
* Participants with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed.
* SR-cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.

Other protocol-defined inclusion/exclusion may apply.

Where this trial is running

Hefei, Anhui and 18 other locations

• Novartis Investigative Site — Hefei, Anhui, China (Recruiting)
• Novartis Investigative Site — Guangzhou, Guangdong, China (Recruiting)
• Novartis Investigative Site — Guangzhou, Guangdong, China (Recruiting)
• Novartis Investigative Site — Nanning, Guangxi, China (Recruiting)
• Novartis Investigative Site — Guiyang, Guizhou, China (Recruiting)
• Novartis Investigative Site — Shijiazhuang, Hebei, China (Recruiting)
• Novartis Investigative Site — Zhengzhou, Henan, China (Recruiting)
• Novartis Investigative Site — Wuhan, Hubei, China (Recruiting)
• Novartis Investigative Site — Nanjing, Jiangsu, China (Recruiting)
• Novartis Investigative Site — Nanchang, Jiangxi, China (Recruiting)
• Novartis Investigative Site — Chengdu, Sichuan, China (Recruiting)
• Novartis Investigative Site — Hangzhou, Zhejiang, China (Recruiting)
• Novartis Investigative Site — Ningbo, Zhejiang, China (Recruiting)
• Novartis Investigative Site — Wenzhou, Zhejiang, China (Recruiting)
• Novartis Investigative Site — Beijing, China (Recruiting)
• Novartis Investigative Site — Beijing, China (Recruiting)
• Novartis Investigative Site — Changsha, China (Recruiting)
• Novartis Investigative Site — Shanghai, China (Recruiting)
• Novartis Investigative Site — Wujiang Nongchang, China (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Graft vs. Host Disease; Chronic Graft vs. Host Disease; Corticosteroid-refractory Chronic Graft vs. Host Disease; cGvHD; GvHD; SR-cGvHD; ruxolitinib; INC424