Itacitinib for the Prevention of Graft Versus Host Disease

NCT04859946 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2020-0971NCI-2021-02784
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies if itacitinib plus standard of care treatment may help prevent graft-versus-host-disease (GVHD) in patients who have received an allogeneic (donor) stem cell transplant. An allogeneic transplant uses blood-making cells from a family member or unrelated donor to remove and replace a patient's abnormal blood cells. Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Giving itacitinib with standard of care treatment after the transplant may stop this from happening.

Conditions

Hematologic and Lymphocytic Disorder

Outcome Measures

Primary Outcomes (1)

• Incidence of acute grade 2-4 graft versus host disease (GVHD)

  The 100-day acute grade 2-4 GvHD rate will be compared between groups using Fisher's exact test. Matched logistic regression techniques will also be considered for this endpoint. The proportion of patients with acute grade 2-4 GVHD at 100 days will be reported, along with the corresponding 95% confidence interval.

  At 100 days after stem cell transplant

Secondary Outcomes (8)

• GVHD-free relapse-free survival

  From day of stem cell transplant to time of grade 3 or 4 acute GVHD or chronic GVHD needing systemic immunosuppression or relapse or death whichever occurs first, assessed at 1 year after stem cell transplant

• Time to neutrophil and platelet engraftment

  Up to 365 days after stem cell transplant

• Overall survival

  From day of stem cell transplant to day of death, assessed up to 365 days after stem cell transplant

• Progression-free survival

  From day of transplant to day of death or disease progression, assessed up to 365 days after stem cell transplant

• Time to relapse

  Up to 365 days after stem cell transplant

Study Arms (1)

Supportive care (itacitinib)

EXPERIMENTAL

CONDITIONING: Patients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, thiotepa IV on day -7, and fludarabine IV over 1 hour on days -6 to -3. STEM CELL TRANSPLANT: Patients undergo stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4. Patients also receive itacitinib PO QD on days 5-60 in the absence of disease progression or unacceptable toxicity. Beginning day 5 after stem cell transplant, patients also receive tacrolimus IV over 24 hours until able to tolerate oral tacrolimus, whereby patients then receive tacrolimus PO BID.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Itacitinib; Drug: Tacrolimus; Drug: Thiotepa

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo stem cell transplant

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Supportive care (itacitinib)

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Supportive care (itacitinib)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Supportive care (itacitinib)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Supportive care (itacitinib)

Itacitinib DRUG

Given PO

Also known as: INCB 039110, INCB-039110, INCB039110

Supportive care (itacitinib)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Supportive care (itacitinib)

Thiotepa DRUG

Given IV

Also known as: 1,1'',1''''-Phosphinothioylidynetrisaziridine, Girostan, N,N'', N''''-Triethylenethiophosphoramide, Oncotiotepa, STEPA, Tepadina, TESPA, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoramide, Thiotef, Tifosyl, TIO TEF, Tio-tef, Triethylene Thiophosphoramide, Triethylenethiophosphoramide, Tris(1-aziridinyl)phosphine sulfide, TSPA, WR 45312

Supportive care (itacitinib)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years to less than or equal to 70 years
• English and non-English speaking patients are eligible
• Karnofsky performance status of at least 70
• Patients with hematological disorders undergoing allogeneic stem cell transplant (ASCT) with conditioning regimen of fractionated busulfan, thiotepa and fludarabine
• Donor will be matched at HLA A, B, C and DR at allele level. Donor will be either HLA-identical sibling or at least 7/8 matched unrelated donor, or a haploidentical related donor available.
• Life expectancy of at least 12 weeks (3 months)
• Direct bilirubin not greater than 1 mg/dL
• Alanine transaminase (ALT) less than or equal 3 x upper limit of normal range
• Creatinine clearance \>/= 60 ml/ min
• Diffusing capacity for carbon monoxide (DLCO) 50% of predicted corrected for hemoglobin
• Left ventricular ejection fraction (LVEF) of at least 50%
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
• Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form (ICF) until at least 30 days after the last dose of study drug. Recommended methods of birth control are:
• Hormonal contraception (birth control pills, patches, or rings)
• Intrauterine device (IUD)

You may not qualify if:

• Patients with acute leukemia in the first complete remission and chronic myeloid leukemia in the first chronic phase during the initial enrollment of 6 patients
• Patients with toxicities (Grade \> 1) unresolved from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery)
• Haploidentical recipients should not have donor-specific antibodies (DSA)
• Active or clinically significant cardiac disease including:
• Congestive heart failure - New York Heart Association (NYHA) \> class II
• Active coronary artery disease
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
• Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before transplant, or myocardial infarction within 6 months before transplant
• Patients with active hepatitis B and C
• Patients with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with safety or with obtaining informed consent or compliance with study procedures

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hematologic Diseases

Interventions

Stem Cell Transplantation; Busulfan; Cyclophosphamide; fludarabine; itacitinib; INCB039110; Tacrolimus; Thiotepa

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Uday R Popat, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 22, 2021
• First Posted: April 26, 2021
• Study Start: January 11, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)