search
Back to results

Itacitinib for the Prevention of Graft Versus Host Disease

Primary Purpose

Hematologic and Lymphocytic Disorder

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Busulfan
Cyclophosphamide
Fludarabine
Itacitinib
Tacrolimus
Thiotepa
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Hematologic and Lymphocytic Disorder

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients 18 years to less than or equal to 70 years
  • 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
  • Human leukocyte antigen (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)
    • Birth control injections
    • Double barrier methods (diaphragm with spermicidal gel or condoms with birth control foam)
    • Sterilization of patient or partner ("tubes tied" or vasectomy)

Exclusion Criteria:

  • Patients with toxicities (Grade > 1) unresolved from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery)

  • 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

Sites / Locations

  • M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Supportive care (itacitinib)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

GVHD-free relapse-free survival
Will be compared between groups using the log-rank test. The method of Kaplan and Meier will be used to estimate the distribution of GVHD-free, relapse-free survival. The estimated probability will be reported at 1 year along with a corresponding 95% confidence interval. In addition, Cox proportional hazards regression models will be fit to this endpoint, considering clinical, demographic, and treatment covariates of interest.
Time to neutrophil and platelet engraftment
Engraftment is defined as the presence of neutrophil recovery by day 28 post stem cell infusion. Neutrophil recovery is defined as a sustained absolute neutrophil count (ANC) > 0.5 x 10^9/L for three consecutive days. Initial platelet recovery is defined as the first date of three consecutive laboratory values obtained for platelet count was >= 20 x 10^9/L AND no platelet transfusions were administered for seven consecutive days immediately preceding this date. Will be calculated from the time of transplant and estimated by the Kaplan-Meier method. Distributions will be compared between patients with matched and mismatched donors via the log-rank test.
Overall survival
Will be calculated from the time of transplant by the method of Kaplan and Meier. Cox proportional hazards regression analysis will be used to assess the association between these survival parameters and clinical and treatment covariates of interest.
Progression-free survival
Will be calculated from the time of transplant by the method of Kaplan and Meier. Cox proportional hazards regression analysis will be used to assess the association between these survival parameters and clinical and treatment covariates of interest.
Time to relapse
Non-relapse mortality
Defined as death from any cause other than relapse disease.
Cumulative incidence of limited, extensive, and moderate to severe chronic GVHD
The cumulative incidence of acute and chronic GVHD with the competing risk of relapse and death without relapse will be estimated using the method of Gooley, and the method of Fine and Gray will be used to model the incidence by disease and clinical characteristics of interest.
Incidence of adverse events
Descriptive statistics will be used to summarize adverse events. Frequency counts and percentages will also be presented of subjects with serious adverse events and adverse events leading to withdrawal. All other safety parameters will be summarized using descriptive statistics or frequency counts. Graphical summaries will be used where appropriate.

Full Information

First Posted
April 22, 2021
Last Updated
August 14, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
Incyte Corporation
search

1. Study Identification

Unique Protocol Identification Number
NCT04859946
Brief Title
Itacitinib for the Prevention of Graft Versus Host Disease
Official Title
Itacitinib to Prevent Graft Versus Host Disease
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 11, 2022 (Actual)
Primary Completion Date
February 2, 2027 (Anticipated)
Study Completion Date
February 2, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
Incyte Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
PRIMARY OBJECTIVE: I. To compare the 100-day acute grade 2-4 GvHD rate to matched controls. SECONDARY OBJECTIVES: I. To compare the 1-year rate of GvHD-free, relapse-free survival to matched controls. II. To assess the time to neutrophil and platelet engraftment. III. To assess the toxicity profile associated with this regimen. IV. To assess the incidence of severe grade 3-4 acute GVHD. V. To assess the incidence of limited, extensive, and moderate to severe chronic GVHD. VI. To assess the incidence of disease relapse. VII. To assess the incidence of non-relapse mortality. VIII. To assess overall survival and progression-free survival. IX. To assess immunosuppression discontinuation rate. TERTIARY OBJECTIVE (CORRELATIVE STUDY): I. Immune recovery and cytokines at various time points pre- and post- transplant OUTLINE: CONDITIONING: Patients receive busulfan intravenously (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 orally (PO) once daily (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 twice daily (BID). After completion of study intervention, patients are followed up at days 100, 180, and 365 after stem cell transplant.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic and Lymphocytic Disorder

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Supportive care (itacitinib)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic
Intervention Description
Undergo stem cell transplant
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fluradosa
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Itacitinib
Other Intervention Name(s)
INCB 039110, INCB-039110, INCB039110
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK 506, Fujimycin, Hecoria, Prograf, Protopic
Intervention Description
Given IV or PO
Intervention Type
Drug
Intervention Name(s)
Thiotepa
Other Intervention Name(s)
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
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Incidence of acute grade 2-4 graft versus host disease (GVHD)
Description
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.
Time Frame
At 100 days after stem cell transplant
Secondary Outcome Measure Information:
Title
GVHD-free relapse-free survival
Description
Will be compared between groups using the log-rank test. The method of Kaplan and Meier will be used to estimate the distribution of GVHD-free, relapse-free survival. The estimated probability will be reported at 1 year along with a corresponding 95% confidence interval. In addition, Cox proportional hazards regression models will be fit to this endpoint, considering clinical, demographic, and treatment covariates of interest.
Time Frame
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
Title
Time to neutrophil and platelet engraftment
Description
Engraftment is defined as the presence of neutrophil recovery by day 28 post stem cell infusion. Neutrophil recovery is defined as a sustained absolute neutrophil count (ANC) > 0.5 x 10^9/L for three consecutive days. Initial platelet recovery is defined as the first date of three consecutive laboratory values obtained for platelet count was >= 20 x 10^9/L AND no platelet transfusions were administered for seven consecutive days immediately preceding this date. Will be calculated from the time of transplant and estimated by the Kaplan-Meier method. Distributions will be compared between patients with matched and mismatched donors via the log-rank test.
Time Frame
Up to 365 days after stem cell transplant
Title
Overall survival
Description
Will be calculated from the time of transplant by the method of Kaplan and Meier. Cox proportional hazards regression analysis will be used to assess the association between these survival parameters and clinical and treatment covariates of interest.
Time Frame
From day of stem cell transplant to day of death, assessed up to 365 days after stem cell transplant
Title
Progression-free survival
Description
Will be calculated from the time of transplant by the method of Kaplan and Meier. Cox proportional hazards regression analysis will be used to assess the association between these survival parameters and clinical and treatment covariates of interest.
Time Frame
From day of transplant to day of death or disease progression, assessed up to 365 days after stem cell transplant
Title
Time to relapse
Time Frame
Up to 365 days after stem cell transplant
Title
Non-relapse mortality
Description
Defined as death from any cause other than relapse disease.
Time Frame
Up to 365 days after stem cell transplant
Title
Cumulative incidence of limited, extensive, and moderate to severe chronic GVHD
Description
The cumulative incidence of acute and chronic GVHD with the competing risk of relapse and death without relapse will be estimated using the method of Gooley, and the method of Fine and Gray will be used to model the incidence by disease and clinical characteristics of interest.
Time Frame
Up to 365 days after stem cell transplant
Title
Incidence of adverse events
Description
Descriptive statistics will be used to summarize adverse events. Frequency counts and percentages will also be presented of subjects with serious adverse events and adverse events leading to withdrawal. All other safety parameters will be summarized using descriptive statistics or frequency counts. Graphical summaries will be used where appropriate.
Time Frame
Up to 365 days after stem cell transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients 18 years to less than or equal to 70 years 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 Human leukocyte antigen (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) Birth control injections Double barrier methods (diaphragm with spermicidal gel or condoms with birth control foam) Sterilization of patient or partner ("tubes tied" or vasectomy) Exclusion Criteria: Patients with toxicities (Grade > 1) unresolved from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery) 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Uday R Popat, MD
Phone
(713) 563-0812
Email
upopat@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Uday R Popat, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Uday R. Popat
Phone
713-745-3055
Email
upopat@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Uday R. Popat

12. IPD Sharing Statement

Learn more about this trial

Itacitinib for the Prevention of Graft Versus Host Disease

We'll reach out to this number within 24 hrs