- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04859946
Itacitinib for the Prevention of Graft Versus Host Disease
Itacitinib to Prevent Graft Versus Host Disease
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Uday R Popat, MD
- Phone Number: (713) 563-0812
- Email: upopat@mdanderson.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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)
- 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)
- Patients enrolled on this study may be enrolled on other IND studies at the discretion of the PI
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Supportive care (itacitinib)
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. |
Given IV
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Undergo stem cell transplant
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of acute grade 2-4 graft versus host disease (GVHD)
Time Frame: At 100 days after stem cell transplant
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
GVHD-free relapse-free survival
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
|
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.
|
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
Time Frame: Up to 365 days after stem cell transplant
|
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. |
Up to 365 days after stem cell transplant
|
Overall survival
Time Frame: From day of stem cell transplant to day of death, assessed up to 365 days after stem cell transplant
|
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.
|
From day of stem cell transplant to day of death, assessed up to 365 days after stem cell transplant
|
Progression-free survival
Time Frame: From day of transplant to day of death or disease progression, assessed up to 365 days after stem cell transplant
|
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.
|
From day of transplant to day of death or disease progression, assessed up to 365 days after stem cell transplant
|
Time to relapse
Time Frame: Up to 365 days after stem cell transplant
|
Up to 365 days after stem cell transplant
|
|
Non-relapse mortality
Time Frame: Up to 365 days after stem cell transplant
|
Defined as death from any cause other than relapse disease.
|
Up to 365 days after stem cell transplant
|
Cumulative incidence of limited, extensive, and moderate to severe chronic GVHD
Time Frame: Up to 365 days after stem cell transplant
|
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.
|
Up to 365 days after stem cell transplant
|
Incidence of adverse events
Time Frame: Up to 365 days after stem cell transplant
|
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.
|
Up to 365 days after stem cell transplant
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Uday R Popat, MD, M.D. Anderson Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Hematologic Diseases
- Graft vs Host Disease
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Calcineurin Inhibitors
- Cyclophosphamide
- Fludarabine
- Tacrolimus
- Thiotepa
- Busulfan
Other Study ID Numbers
- 2020-0971 (Other Identifier: M D Anderson Cancer Center)
- NCI-2021-02784 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hematologic and Lymphocytic Disorder
-
Fred Hutchinson Cancer CenterRecruitingNon-Neoplastic Hematologic and Lymphocytic DisorderUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); National Institutes of Health (NIH)RecruitingHematopoietic and Lymphoid Cell Neoplasm | Non-Neoplastic Hematologic and Lymphocytic DisorderUnited States
-
University of Michigan Rogel Cancer CenterCompletedHematologic Neoplasms | Graft vs Host Disease | Non-Neoplastic Hematologic and Lymphocytic DisorderUnited States
-
Roswell Park Cancer InstituteCompletedMalignant Neoplasm | Parent | Hematologic and Lymphocytic Disorder | GuardianUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); National Heart, Lung, and Blood Institute... and other collaboratorsCompletedNon-Neoplastic Hematologic and Lymphocytic DisorderUnited States
-
Fred Hutchinson Cancer CenterRecruitingHematopoietic and Lymphoid System Neoplasm | Hematologic and Lymphocytic DisorderUnited States
-
M.D. Anderson Cancer CenterCelgene CorporationTerminatedHematologic DisorderUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)RecruitingHematopoietic and Lymphoid Cell Neoplasm | Malignant Neoplasm | Immune System Disorder | Healthy Subject | Hematologic and Lymphocytic DisorderUnited States
-
Hangzhou Zenshine Pharmaceuticals Co., Ltd.TerminatedChronic Lymphocytic Leukemia | Small Lymphocytic Lymphoma | Non-hodgkin LymphomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)WithdrawnHematopoietic and Lymphoid Cell Neoplasm | Hematologic and Lymphocytic Disorder | Allogeneic Stem Cell Transplant RecipientUnited States
Clinical Trials on Cyclophosphamide
-
Children's Hospital Los AngelesLucile Packard Children's HospitalTerminatedMetabolic Diseases | Stem Cell Transplantation | Chronic Granulomatous Disease | Bone Marrow Transplantation | Thalassemia | Wiskott-Aldrich Syndrome | Genetic Diseases | Peripheral Blood Stem Cell Transplantation | Pediatrics | Diamond-Blackfan Anemia | Allogeneic Transplantation | Combined Immune Deficiency | X-linked Lymphoproliferative Disease
-
Medical College of WisconsinNational Cancer Institute (NCI); National Heart, Lung, and Blood Institute... and other collaboratorsCompletedAnemia, AplasticUnited States
-
Columbia UniversityUnknownSevere Combined Immunodeficiency | Fanconi Anemia | Bone Marrow Failure | OsteopetrosisUnited States
-
Mahidol UniversityTerminatedRenal Insufficiency | InfectionThailand
-
National Cancer Institute, NaplesImmatics Biotechnologies GmbH; CureVac; European Commission -FP7-Health-2013-Innovation-1CompletedHepatocellular CarcinomaBelgium, Germany, Italy, Spain, United Kingdom
-
Eisai Inc.CompletedBreast Cancer | Ovarian Cancer | Prostate Cancer | Colon Cancer | Renal CancerUnited States
-
Centre Oscar LambretCompleted
-
Baylor Research InstituteCompletedMalignant Melanoma Stage IVUnited States
-
University of Turin, ItalyUnknown
-
Merck KGaA, Darmstadt, GermanyCompleted