Itacitinib for the Prevention of Graft Versus Host Disease in Patients Undergoing Donor Stem Cell Transplantation

NCT04127721 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 2018-0505NCI-2019-05753
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well itacitinib works in preventing graft versus host disease in patients with blood disorders undergoing donor stem cell transplantation. A donor transplantation uses blood-making cells from a family member or unrelated donor to remove and replace abnormal blood cells. Graft versus host disease is a reaction of the donor's immune cells against the patient's body. Itacitinib plus standard treatment may help prevent graft versus host disease in patients who have received a donor stem cell transplantation.

Conditions

Allogeneic Stem Cell Transplant Recipient; Hematologic and Lymphocytic Disorder; Hematopoietic and Lymphoid Cell Neoplasm

Outcome Measures

Primary Outcomes (1)

• Graft versus host disease (GVHD)-free/relapse free survival rate

  The proportion of patients who are alive without disease relapse of GVHD at one year will be reported, along with the corresponding 95% confidence interval. Logistic regression will be used to assess the association between success and clinical and treatment covariates of interest.

  At 1 year

Secondary Outcomes (9)

• Time to neutrophil engraftment

  Up to day 42

• Time to platelet engraftment

  Up to day 42

• To assess the incidence of non-relapse mortality

  At day 100

• To assess the toxicity profile associated with this regimen

  Up to 1 year

• To assess the incidence of acute and chronic GVHD.

  Up to 1 year

Other Outcomes (2)

• Immune recovery and cytokines

  Up to 1 year

• Deoxyribonucleic acid (DNA) damage studies

  Up to 1 year

Study Arms (1)

Prevention (itacitinib, busulfan, fludarabine, ASCT)

EXPERIMENTAL

CONDITIONING CHEMOTHERAPY: Patients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity. ALLOGENEIC STEM CELL TRANSPLANTATION: Patients undergo ASCT on day 0. GVHD PROPHYLAXIS: Patients receive itacitinib PO QD on days -21 to 80. Patients with no evidence of GVHD at day 80 receive a tapered dose of itacitinib until day 90. Patients also receive tacrolimus IV then PO BID for 3 months when able, and methotrexate IV over 30 minutes on days 1, 3, and 6 (day 11 also for patients with a matched unrelated donor).

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

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo ASCT

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

Prevention (itacitinib, busulfan, fludarabine, ASCT)

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

Prevention (itacitinib, busulfan, fludarabine, ASCT)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Prevention (itacitinib, busulfan, fludarabine, ASCT)

Itacitinib DRUG

Given PO

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

Prevention (itacitinib, busulfan, fludarabine, ASCT)

Methotrexate DRUG

Given IV

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Prevention (itacitinib, busulfan, fludarabine, ASCT)

Tacrolimus DRUG

Given IV and PO

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

Prevention (itacitinib, busulfan, fludarabine, ASCT)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Karnofsky performance status of at least 70
• Patients with hematological disorders undergoing ASCT with conditioning regimen of timed sequential busulfan and fludarabine
• Human leukocyte antigen (HLA)-identical sibling or 8/8 matched unrelated 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
• Serum creatinine less than 1.5 x the upper limit of normal range and creatinine clearance greater than 50 ml/min
• Diffusing capacity for carbon monoxide (DLCO) 65% of predicted corrected for hemoglobin
• Left ventricle 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 until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate

You may not qualify if:

• Patients with a comorbidity score \> 3. The principal investigator is the final arbiter of eligibility and enrollment of patients with comorbidity score \> 3 and may permit enrollment of these patients on individual basis
• 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 uncontrolled infections
• Patients with active hepatitis B and C

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hematologic Diseases; Hematologic Neoplasms

Interventions

Busulfan; fludarabine; itacitinib; INCB039110; Methotrexate; merphos; Tacrolimus

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones

Study Officials

• Uday R Popat

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 30, 2019
• First Posted: October 16, 2019
• Study Start: September 22, 2020
• Primary Completion: September 22, 2020
• Study Completion: September 22, 2020
• Last Updated: October 29, 2020

Record last verified: 2020-10

Locations

US (1)