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NCT03846479

Itacitinib for Low Risk GVHD

Completed Phase 2 Results posted Last updated 6 February 2023
What this trial tests

Phase 2 trial testing Itacitinib in Low Risk Acute Graft-versus-host Disease in 70 participants. Completed in 11 May 2022.

Timeline
25 March 2019
Primary endpoint
7 May 2021
11 May 2022

Quick facts

Lead sponsorJohn Levine
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment70
Start date25 March 2019
Primary completion7 May 2021
Estimated completion11 May 2022
Sites14 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

John Levine

Who can join

Adults 12 to 75, any sex, with Low Risk Acute Graft-versus-host Disease or Graft-versus-host-disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients Who Achieve CR or PR by Day 28 of Treatment Primary · Day 28

Number of patients who achieve CR or PR by day 28 of treatment with itacitinib without the addition of any other systemic GVHD treatment including steroids. Complete Response (CR): All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR on day 28, the patient must be in CR on that day and have had no intervening additional GVHD therapy. Partial Response (PR): An improvement in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR on day 28, the patient must be in PR on that day and have had no intervening

GroupValue95% CI
Low Risk GVHD Patients Treated62
Number of Participants Who Developed Steroid Refractory GVHD Primary · Day 28

Number of participants who developed steroid refractory GVHD within 28 days of starting steroids. Steroid-refractory GVHD (defined as GVHD that worsens (increase by one or more grade) after 3 days, or fails to respond to treatment within 7 days (for GVHD grade III) or 14 days (for GVHD grade II) or 2nd line therapy beyond systemic steroid treatment is begun within 28 days of starting steroids.

GroupValue95% CI
Low Risk GVHD Patients Treated1
Number of Participants With Serious Infectious Secondary · Day 90

Number of participants who developed serious infections by day 90. Serious infectious complications is defined as any viral and bacterial infections requiring treatment and proven fungal infections.

GroupValue95% CI
Low Risk GVHD Patients Treated19
Number of Participants Alive at 6 Months and 1 Year Secondary · 6 months and 1 year

Number of overall survival (OS), defined as the duration from the date of diagnosis to death or last follow-up, with no restriction on the cause of death.

6 months
GroupValue95% CI
Low Risk GVHD Patients Treated66
1 year
GroupValue95% CI
Low Risk GVHD Patients Treated62
Number of Participants With Non-relapse Mortality (NRM) Secondary · 6 months and 1 year

Number of participants with non-relapse mortality (NRM) at 6 months and 1 year

6 months
GroupValue95% CI
Low Risk GVHD Patients Treated2
1 year
GroupValue95% CI
Low Risk GVHD Patients Treated3
Number of Participants Who Relapsed Secondary · 6 months and 1 year

Number of participants who relapsed by 6 months and by 1 year

6 months
GroupValue95% CI
Low Risk GVHD Patients Treated8
1 year
GroupValue95% CI
Low Risk GVHD Patients Treated12
Number of Participants Who Developed Chronic GVHD Secondary · 1 year

Number of participants who developed chronic GVHD requiring systemic treatment at 1 year

GroupValue95% CI
Low Risk GVHD Patients Treated18
Cumulative Steroid Dose Secondary · Day 28

Cumulative steroid dose (over 4 weeks) in patients who receive steroids as second line therapy

GroupValue95% CI
Low Risk GVHD Patients Treated1.9± 0.6

Adverse events — posted to ClinicalTrials.gov

Time frame: 90 days for Adverse Events 1 year for All-Cause Mortality. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Low Risk GVHD Patients Treated
Serious: 23/70 (33%)
Deaths: 8/70

Serious adverse events (24 terms)

ReactionSystemLow Risk GVHD Patients Tre…
RelapseNeoplasms benign, malignant and unspecified (incl cysts and polyps)
GVHDImmune system disorders
Catheter Related InfectionInfections and infestations
FeverGeneral disorders
C. Difficile InfectionInfections and infestations
SepsisInfections and infestations
BK CystitisInfections and infestations
BacteremiaInfections and infestations
Febrile NeutropeniaBlood and lymphatic system disorders
DysuriaRenal and urinary disorders
Subarachnoid HemorrhageInjury, poisoning and procedural complications
Adenovirus Hemorrhagic CystitisInfections and infestations
Acute Kidney InjuryRenal and urinary disorders
SyncopeNervous system disorders
VomitingGastrointestinal disorders
Blood Bilirubin IncreasedInvestigations
HypertensionVascular disorders
SARS-CoV-2 InfectionInfections and infestations
EBV InfectionInfections and infestations
Upper Respiratory InfectionInfections and infestations
Lung InfectionInfections and infestations
CMV ViremiaInfections and infestations
Suicidal IdeationPsychiatric disorders
FallInjury, poisoning and procedural complications
Other adverse events (20 terms — click to expand)

ReactionSystemLow Risk GVHD Patients Tre…
AnemiaBlood and lymphatic system disorders
Platelet Count DecreasedInvestigations
White Blood Cell DecreasedInvestigations
Neutrophil Count DecreasedInvestigations
Alanine Aminotransferase IncreasedInvestigations
HypertensionVascular disorders
CMV InfectionInfections and infestations
Lymphocyte Count DecreasedInvestigations
Arthralgia and/or MyalgiaMusculoskeletal and connective tissue disorders
SyncopeNervous system disorders
HypokalemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
HypotensionVascular disorders
Reversible Posterior Leukoencephalopathy SyndromeNervous system disorders
Thrombotic MicroangiopathyVascular disorders
HeadacheNervous system disorders
HypertriglyceridemiaMetabolism and nutrition disorders
Urinary Tract InfectionInfections and infestations
EBV InfectionInfections and infestations
Multifocal PneumoniaInfections and infestations

Most-reported serious reactions: Relapse, GVHD, Catheter Related Infection, Fever, C. Difficile Infection, Sepsis, BK Cystitis, Bacteremia.

Data from ClinicalTrials.gov NCT03846479 adverse events section.

Sponsor's own description

Graft-versus-host disease (GVHD) is treated with high doses of systemic steroids which can lead to serious complications. A new blood test can identify patients whose GVHD is most likely to respond to well to treatment (low risk GVHD). This study will test whether patients with low risk GVHD can be successfully treated without steroids. Patients who participate with this study will be treated with itacitinib instead of steroids. Itacitinib is an experimental drug with an excellent safety record and appears to have activity as a GVHD treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer.
    Xue C, Yao Q, Gu X, Shi Q, et al · · 2023 · cited 399× · PMID 37208335 · DOI 10.1038/s41392-023-01468-7
  2. Emerging Topical and Systemic JAK Inhibitors in Dermatology.
    Solimani F, Meier K, Ghoreschi K. · · 2019 · cited 199× · PMID 31849996 · DOI 10.3389/fimmu.2019.02847
  3. JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens.
    Hu Q, Bian Q, Rong D, Wang L, et al · · 2023 · cited 190× · PMID 36911202 · DOI 10.3389/fbioe.2023.1110765
  4. JAK-STAT signaling in human disease: From genetic syndromes to clinical inhibition.
    Luo Y, Alexander M, Gadina M, O'Shea JJ, et al · · 2021 · cited 92× · PMID 34625141 · DOI 10.1016/j.jaci.2021.08.004
  5. A Decade of JAK Inhibitors: What Have We Learned and What May Be the Future?
    Liu C, Kieltyka J, Fleischmann R, Gadina M, et al · · 2021 · cited 49× · PMID 34180156 · DOI 10.1002/art.41906
  6. Prevention and Treatment of Acute Graft-versus-Host Disease in Children, Adolescents, and Young Adults.
    Gatza E, Reddy P, Choi SW. · · 2020 · cited 41× · PMID 31931115 · DOI 10.1016/j.bbmt.2020.01.004
  7. Kinase Inhibition as Treatment for Acute and Chronic Graft-<i>Versus</i>-Host Disease.
    Braun LM, Zeiser R. · · 2021 · cited 35× · PMID 34868001 · DOI 10.3389/fimmu.2021.760199
  8. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIb. The 2020 Preemptive Therapy Working Group Report.
    Pidala J, Kitko C, Lee SJ, Carpenter P, et al · · 2021 · cited 35× · PMID 33836313 · DOI 10.1016/j.jtct.2021.03.029

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