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

NCT ID: NCT04127721

Last Updated: 2020-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-22

Study Completion Date

2020-09-22

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVE:

I. To estimate the graft-versus (vs.) host disease-free/relapse free survival (GRFS) rate of itacitinib used as prophylaxis to prevent graft versus host disease (GVHD) after allogeneic stem cell transplantation (ASCT) at one year.

SECONDARY OBJECTIVES:

I. To assess the time to neutrophil and platelet engraftment and compare between matched and unmatched donors.

II. To assess safety of itacitinib as measured by non-relapse mortality (NRM) at day 100.

III. To assess the toxicity profile associated with this regimen. IV. To assess the incidence of acute and chronic GVHD. V. To assess the incidence of disease relapse. VI. To assess the incidence of non-relapse mortality. VII. To assess overall survival and progression-free survival. VIII. To assess the incidence of withdrawal syndrome in patients with myelofibrosis.

TERTIARY OBJECTIVES (CORRELATIVE STUDIES):

I. To study immune recovery and cytokines at various time points pre and post-transplant.

II. To study deoxyribonucleic acid (DNA) damage studies in various cells post-transplant.

OUTLINE:

CONDITIONING CHEMOTHERAPY: Patients receive busulfan intravenously (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 orally (PO) once daily (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 twice daily (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).

After completion of study treatment, patients are followed up at 100 days, 6 months, and 1 year.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Prevention (itacitinib, busulfan, fludarabine, ASCT)

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).

Group Type EXPERIMENTAL

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo ASCT

Busulfan

Intervention Type DRUG

Given IV

Fludarabine

Intervention Type DRUG

Given IV

Itacitinib

Intervention Type DRUG

Given PO

Methotrexate

Intervention Type DRUG

Given IV

Tacrolimus

Intervention Type DRUG

Given IV and PO

Interventions

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Allogeneic Hematopoietic Stem Cell Transplantation

Undergo ASCT

Intervention Type PROCEDURE

Busulfan

Given IV

Intervention Type DRUG

Fludarabine

Given IV

Intervention Type DRUG

Itacitinib

Given PO

Intervention Type DRUG

Methotrexate

Given IV

Intervention Type DRUG

Tacrolimus

Given IV and PO

Intervention Type DRUG

Other Intervention Names

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Allogeneic Hematopoietic Cell Transplantation Allogeneic Stem Cell Transplantation HSC HSCT 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 Fluradosa INCB 039110 INCB-039110 INCB039110 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 FK 506 Fujimycin Hecoria Prograf Protopic

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Uday R Popat

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2019-05753

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-0505

Identifier Type: OTHER

Identifier Source: secondary_id

2018-0505

Identifier Type: -

Identifier Source: org_study_id