A Study of Itacitinib for the Treatment of Chronic Graft Versus Host Disease (cGVHD)

NCT04200365 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: BMT29
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 5

Brief Summary

This study is being done in patients who have been receiving corticosteroids or other immunosuppressive therapies for the treatment of cGVHD for at least 6 months. The purpose of this study is to find out if itacitinib in combination with corticosteroids or other immunosuppressive therapies is safe and effective in people with cGVHD.

Conditions

Chronic Graft-versus-host-disease

Keywords

Chronic Graft-versus-host-disease; Allogeneic hematopoietic stem cell transplant; Corticosteroids; Immunosuppressive therapies

Outcome Measures

Primary Outcomes (1)

• cGVHD Overall Response Rate (ORR) at 6 Months on Treatment

  Defined as the rate of participants with a cGVHD response of complete response (CR) or partial response (PR) after 6 months of treatment with Itacitinib as defined by 2014 National Institutes of Health Consensus Development Project on Clinical Trials in cGVHD. CR is defined as resolution of all manifestations of cGVHD in each organ or site. PR is defined as the improvement in at least one organ or site without progression in any other organ or site.

  Response assessed Day 1 of every cycle up until the end of treatment, up to 24 months. This outcome measure is the ORR for all patients once they have been on treatment for 6 months.

Secondary Outcomes (6)

• Number of Participants That Can Withdraw or Decrease Steroids

  From first dose of itacitinib until end of study treatment, up to 24 months

• Overall Survival

  Every 3 months for 1 year after last dose of study treatment, up to 29 months.

• Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of Itacitinib

  Safety will be assessed from the time that informed consent is signed until 30 days after the last dose of study treatment, up to 25 months.

• Number of Participants With Improvement in Quality of Life Per the Lee Symptom Scale

  Quality of life will be assessed prior during screening and end of treatment, up to 24 months of treatment. Participants showing improvement in LSS score from Screening to End of Treatment are shown here.

• Number of Participants With Recurrence or Progression of cGVHD

  cGVHD status will be assessed at cycle 1 day 1, day 1 of every cycle and at the end of treatment, up to 24 months

Study Arms (1)

Itacitinib

EXPERIMENTAL

Drug: Itacitinib

Interventions

Itacitinib DRUG

Itacitinib will be administered orally once daily for up to 24 months.

Also known as: INCB039110 adipate

Itacitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent signed by the patient or legal guardian prior to any study-related screening procedures
• Patients who have undergone allo-hematopoietic stem cell transplant(s) (HSCT) 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 non-myeloablative, myeloablative, and reduced intensity conditions are eligible.
• Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria:
• Moderate cGVHD: at least 1 organ (except lung) with a score of 2, ≥3 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
• cGVHD must be refractory to steroids defined by at least one criteria:
• Patient is refractory to glucocorticoid therapy at screening: ongoing treatment with prednisone equivalent ≥0.20 mg/kg/day x 4 weeks (wks) at screening and organ progression documented 4 wks after the initiation of this regimen
• Patient is dependent on glucocorticoid therapy at screening: treatment with a prednisone equivalent mean dose ≥0.20 mg/kg/day received for 12 wks at screening
• Patient is intolerant to glucocorticoids at screening: ongoing treatment with prednisone equivalent ≥0.20 mg/kg/day x 4 wks at screening and presence of at least one documented glucocorticoid toxicity
• Evidence of myeloid and platelet engraftment (absolute neutrophil count ˃1,000/mm\^3 and platelet count ˃25,000/mm\^3). Use of growth factors or platelet transfusions is not allowed within 7 days before screening of laboratory assessment.
• Patients must currently be receiving systemic or other immunosuppressive therapies for the treatment of cGVHD for a duration of ˃6 months prior to start of study treatment
• Patients must be able to swallow and retain oral medication
• Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
• Adequate hematologic function
• Adequate renal function: creatinine clearance ≥30 mL/min measured or calculated by Cockcroft Gault equation

You may not qualify if:

• Receiving concomitant JAK inhibitor for cGVHD; prior treatment with a JAK inhibitor for acute GVHD is permitted if treatment was stopped more than 60 days prior to study start. Patients are eligible if JAK inhibitors for treatment of cGVHD are stopped due to side effects and not due to refractoriness.
• Treatment with any other investigational agent, device, or procedure, within 28 days (or 5 half-lives, whichever is longer) of enrollment. For previous study drugs where 5 half-lives is ≤28 days, a minimum of 10 days between termination of that study drug and administration of itacitinib is required.
• Presence of current secondary malignancies with the exception of previously treated in situ carcinoma, cervical carcinoma Stage 1B or less, and noninvasive basal cell or squamous cell skin carcinoma.
• Pregnant or nursing (lactating) women
• Patients with relapsed primary malignancy, or who have been treated for relapse after the allo-HSCT was performed
• History of progressive multifocal leukoencephalopathy
• Evidence of the following infections:
• Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Known HIV infection
• Active tuberculosis infection that developed after allo-HSCT
• Active viral infection confirmed by polymerase chain reaction for the BK virus ( a polyoma virus), cytomegalovirus, Epstein-Barr virus, and human herpes virus 6
• Active hepatitis B virus (HBV) or hepatitis C virus that requires treatment, or at risk for HBV reactivation (i.e., positive HBsAg)
• Severe organ dysfunction unrelated to underlying GVHD including:
• Cholestatic disorders or unresolved veno-occlusive disease of the liver (persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction)
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral itacitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowl resection)

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Incyte Corporation: collaborator

Study Sites (5)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

South Austin Medical Center

Austin, Texas, 78704, United States

Location

Texas Oncology - Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

itacitinib

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Results Point of Contact

• Title: Sarah Cannon Development Innovations, LLC
• Organization: Sarah Cannon Development Innovations, LLC

SCRI.InnovationsMedical@scri.com

844-710-6157

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 16, 2019
• Study Start: June 5, 2020
• Primary Completion: September 7, 2023
• Study Completion: September 7, 2023
• Last Updated: November 6, 2024
• Results First Posted: November 6, 2024

Record last verified: 2024-08

Locations

US (5)