Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

Rare Diseases

Syndrome

Hematologic Neoplasms

Bronchiolitis

Graft vs Host Disease

Bronchiolitis Obliterans Syndrome

Bronchiolitis Obliterans

Hematologic Diseases

Bronchitis

Communicable Diseases

Respiratory Tract Infections

Bronchial Diseases

Respiratory Tract Diseases

Lung Diseases, Obstructive

Lung Diseases

Pneumonia

Organizing Pneumonia

Chronic Graft Versus Host Disease

Homologous Wasting Disease

Bronchiolitis Obliterans Organizing Pneumonia

Ruxolitinib twice daily treatment, combined with steroids 1mg/kg/day for two weeks, and tampering 0.25 mg/kg/day every week

Ruxolitinib

Yi Luo, M.D.

Yibo Wu, M.D.

Lung is one of the target organs in chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Bronchiolitis obliterans syndrome (BOS) after allo-HSCT was a clinical syndrome characterized by persistent airflow restriction which is the result of lung cGVHD. BOS is one of the main causes of late mortality after allo-HSCT, severely restricting the daily activities and respiratory function of patients. It limits the quality of life and increased the non-relapse mortality (NRM) after allo-HSCT. Currently, the first-line treatment for BOS is FAM ( oral fluticasone, azithromycin and montelukast). However, more than 50% of patients develop as steroids resistant (SR)-BOS, and SR-BOS has a poor prognosis and irreversible impaired lung function. Ruxolitinib is an effective drug in the treatment of SR-cGVHD. This is a phase Ⅱ prospective clinical study to explore the efficacy and safety of ruxolitinib as a first-line treatment for newly diagnosed BOS after allo-HSCT.

The incidence of chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was 30%-70%, Which extremely limited the quality of life and the survival of patients after allo-HSCT. Lung is one of the target organs in cGVHD after allo-HSCT. Bronchiolitis obliterans syndrome (BOS) after allo-HSCT was a clinical syndrome characterized by persistent airflow restriction which is the result of lung cGVHD. BOS is one of the main causes of late mortality after allo-HSCT, severely restricting the daily activities and respiratory function of patients. It limits the quality of life and increased the non-relapse mortality (NRM) after allo-HSCT. Currently, the first-line treatment for BOS is FAM ( oral fluticasone, azithromycin and montelukast). However, more than 50% of patients develop as steroids resistant (SR)-BOS, and SR-BOS has a poor prognosis and irreversible impaired lung function. Ruxolitinib is an effective drug in the treatment of SR-cGVHD. This is a phase Ⅱ prospective clinical study to explore the efficacy and safety of ruxolitinib as a first-line treatment for newly diagnosed BOS after allo-HSCT.

Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome

Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation

The proportion of participants with a sustained, absolute FEV1 increase by ≥ 10% after 3 months of treatment with ruxolitinib (compared to baseline measure prior to study enrollment)

The proportion of participants who do not experience a sustained, absolute decrease in FEV1 by ≥ 10% after 3 months of treatment with ruxolitinib (compared to baseline measure prior to study enrollment)

The proportion of participants with a sustained, absolute FEV1 increase by ≥ 10% after treatment with ruxolitinib (compared to baseline measure prior to study enrollment)

mprovements in chronic GVHD organ specific manifestations will be categorized according to the NIH chronic GVHD consensus criteria.

The proportion of patients survival at two years after enrollment of ruxolitinib treatment

Participants alive without cGVHD progression are censored at the date of last disease evaluation

Adverse events are graded according to Common Terminology Criteria for Adverse Events (CTCAE v4)

The change of systemic corticosteroid dose over time during the treatment of BOS

Second Affiliated Hospital, School of Medicine, Zhejiang University

Zhejiang Provincial People's Hospital

The First Affiliated Hospital of Zhejiang Chinese Medical University

Sir Run Run Shaw Hospital

First Affiliated Hospital of Wenzhou Medical University

Ningbo No. 1 Hospital

The Affiliated People's Hospital of Ningbo University

Jinhua Central Hospital

Taizhou Hospital

Union hospital of Fujian Medical University

Xiangya Hospital of Central South University

First Affiliated Hospital of Zhejiang University

Patients with hematologic malignancies following allogeneic hematopoietic stem cell transplantation treatment

collecting 15ml peripheral blood samples at -7 days before transplantation and+28 days, +100 days, +1 years, +2 years after transplantation

blood sample

collecting 50mg fresh stool samples at -7 days before transplantation and+28 days, +100 days, +1 years, +2 years after transplantation

stool sample

Baodong Ye, MD

Yang Xu, MD

Haowen Xiao, MD

Jianping Lan, MD

Huixian Hu, MD

Guifang Ouyang, MD

Ying Chen, MD

Ying Lu, MD

Yi Chen, MD

Previous studies had found that the microbe in intestinal after allogeneic hematopoietic cell transplantation(allo-HSCT) were closely associated with overall survival and post-transplantation complications, especially graft versus host disease (GVHD).Due to the limited data on the association of microbiota composition with chronic GVHD(cGVHD) after allogeneic hematopoietic stem cell transplantation, the relationship between microbiota composition and post-transplantation complications, especially cGVHD, needs to be further evaluated.Detailed studies of the microbiome and host immune system will lead to the discovery of microbiome markers for early identification of patients at high risk for cGVHD. This may regulate patients' gut microbiota in an individualized manner to achieve optimal treatment outcomes while avoiding severe post-transplant cGVHD. We will operate a prospective, multicenter, nonrandomized, observational study. Patients will be asked to provide blood and stool samples during allo-HSCT.

Previous studies had found that the microbe in intestinal after allogeneic hematopoietic cell transplantation(allo-HSCT) were closely associated with overall survival and post-transplantation complications, especially graft versus host disease (GVHD).Due to the limited data on the association of microbiota composition with chronic GVHD(cGVHD) after allogeneic hematopoietic stem cell transplantation, the relationship between microbiota composition and post-transplantation complications, especially cGVHD, needs to be further evaluated.Detailed studies of the microbiome and host immune system will lead to the discovery of microbiome markers for early identification of patients at high risk for cGVHD. This may regulate patients' gut microbiota in an individualized manner to achieve optimal treatment outcomes while avoiding severe post-transplant cGVHD. We will operate a prospective, multicenter, nonrandomized, observational study. Patients will be asked to provide blood and stool samples during allo-HSCT. This blood will be used for plasma banking for further analysis, including miR, chemokine and metabonomics detection. Stool will be used for microbiome studies - isolation of total DNA/RNA and 16S rRNA gene sequencing for bacterial taxonomic classification. Furthermore, metagenomic sequencing and subsequent taxonomic and functional classification of microbial genes will be used.

This blood will be used for plasma banking for further analysis, including miR and chemokine detection. Stool will be used for microbiome studies - isolation of total DNA/RNA and 16S rRNA gene sequencing for bacterial taxonomic classification. Furthermore, metagenomic sequencing and subsequent taxonomic and functional classification of microbial genes will be used.

The Association of Microbiota Composition With cGVHD After Allo-HSCT

The Association of Microbiota Composition With Chronic Graft Versus Host Disease

Microbial changes of stool will be assessed before, at time and after hematopoietic cell transplantation

To assess microbial changes with toxicity of therapy

To correlate microbial changes with the quality of life which measured by Short Form 36 (SF-36) and and Functional Assessment of Chronic Illness Therapy with BMT subscale (FACT-BMT)

To correlate microbial changes with the patients nutrition. Clinical and biological nutritional assessments included anthropometric measurements, serum nutritional proteins, body composition assessed by bioelectrical impedance, and upper-limb muscle strength (MS) measured by dynamometry.

Principal Investigator

Diseases and Abnormalities at or Before Birth

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Thalassemia

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Neoplasms by Histologic Type

Myeloproliferative Disorders

Bone Marrow Diseases

Anemia

Hemolysis

Anemia, Hemolytic

Anemia, Hemolytic, Congenital

Hemoglobinopathies

Genetic Diseases, Inborn

Bone Marrow Neoplasms

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Gastrointestinal Agents

Panobinostat

Lactitol

Histone Deacetylase Inhibitors

Enzyme Inhibitors

All participants will receive either ruxolitinib monotherapy or ruxolitinib in combination with panobinostat, at the same dose/schedule that they were taking in the parent study.

ruxolitinib tablets or pediatric oral solution - participants continue ruxolitinib as they received in parent study

ruxolitinib

panobinostat capsules - participants to continue receiving panobinostat in combination with ruxolitinib as per the parent study

panobinostat

Novartis Pharmaceuticals

This is a long term safety study for patients that have been treated with either ruxolitinib or a combination of ruxolitinib with panobinostat, on a Novartis or Incyte sponsored study, who have been judged by the study Investigator to benefit from ongoing treatment.

This roll-over protocol allows patients from multiple protocols, who are still receiving clinical benefit, to continue their treatment in one study that covers multiple indications. The population for the roll-over study should be consistent with the population defined in the parent studies. The primary eligibility criteria for a patient to enter the roll-over protocol is the participation and completion of a Novartis or Incyte study with ruxolitinib monotherapy or combination of ruxolitinib and panobinostat. Efficacy parameters will not be measured; however safety data and an evaluation of clinical benefit will be collected.

CINC424A2X01B Rollover Protocol

Open Label, Multi-center, Phase IV Study of Ruxolitinib or Ruxolitinib and Panobinostat Combination, for Patients Who Have Completed Prior Global Novartis or Incyte Sponsored Studies

The incidence of treatment-emergent AEs and SAEs (new or worsening from baseline) will be summarized by system organ class and/or preferred term, severity (based on CTCAE grades).

The analysis of clinical benefit will be descriptive only and cannot be compared to efficacy results of other studies. In addition, as clinical benefit was only added in protocol amendment 1, it may not be available for all participants.

AEs and SAEs for participants in the Safety group will be listed and summarized by treatment group (ruxolitinib monotherapy / ruxolitinib + panobinostat combination)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome	NCT05413356	Bronchiolitis O... Hematologic Mal...	Ruxolitinib	18 Years - 65 Years	First Affiliated Hospital of Zhejiang University
The Association of Microbiota Composition With cGVHD After Allo-HSCT	NCT05355675	Hematopoietic S... Hematologic Mal... Chronic Graft-v... Complication	blood sample stool sample	18 Years - 65 Years	First Affiliated Hospital of Zhejiang University
CINC424A2X01B Rollover Protocol	NCT02386800	Primary Myelofi... Polycythemia Ve... Graft Versus Ho... Acute Myeloid L... Thalassemia	ruxolitinib panobinostat	1 Month -	Novartis
The Association of Microbiota Composition With cGVHD After Allo-HSCT	NCT05355675	Hematopoietic S... Hematologic Mal... Chronic Graft-v... Complication	blood sample stool sample	18 Years - 65 Years	First Affiliated Hospital of Zhejiang University

Spots Global Cancer Trial Database for chronic graft versus host disease