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

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ClinicalTrials.gov Identifier: NCT04127721
Recruitment Status : Withdrawn (0 ACTUAL Enrollment must have Overall Recruitment Status)
First Posted : October 16, 2019
Last Update Posted : October 29, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Allogeneic Stem Cell Transplant Recipient Hematologic and Lymphocytic Disorder Hematopoietic and Lymphoid Cell Neoplasm Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Drug: Busulfan Drug: Fludarabine Drug: Itacitinib Drug: Methotrexate Drug: Tacrolimus Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Itacitinib to Prevent Graft Versus Host Disease
Actual Study Start Date : September 22, 2020
Actual Primary Completion Date : September 22, 2020
Actual Study Completion Date : September 22, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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).

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo ASCT
Other Names:
  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HSC
  • HSCT

Drug: Busulfan
Given IV
Other Names:
  • 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

Drug: Fludarabine
Given IV
Other Name: Fluradosa

Drug: Itacitinib
Given PO
Other Names:
  • INCB 039110
  • INCB-039110
  • INCB039110

Drug: Methotrexate
Given IV
Other Names:
  • 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

Drug: Tacrolimus
Given IV and PO
Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic




Primary Outcome Measures :
  1. Graft versus host disease (GVHD)-free/relapse free survival rate [ Time Frame: At 1 year ]
    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.


Secondary Outcome Measures :
  1. Time to neutrophil engraftment [ Time Frame: Up to day 42 ]
    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 long-rank test.

  2. Time to platelet engraftment [ Time Frame: Up to day 42 ]
    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 long-rank test.

  3. To assess the incidence of non-relapse mortality [ Time Frame: At day 100 ]
  4. To assess the toxicity profile associated with this regimen [ Time Frame: Up to 1 year ]
  5. To assess the incidence of acute and chronic GVHD. [ Time Frame: Up to 1 year ]
  6. Time to disease relapse [ Time Frame: Up to 1 year ]
    Will be modeled using Cox proportional hazards regression models, considering clinical, demographic, and treatment covariates of interest.

  7. Incidence of non-relapse mortality [ Time Frame: Up to 1 year ]
    Will be modeled using Cox proportional hazards regression models, considering clinical, demographic, and treatment covariates of interest. Will be assessed in a competing risks framework, with similar analyses performed.

  8. To assess overall survival and progression-free survival. [ Time Frame: From day of transplant until day of death, assessed up to 1 year ]
  9. Incidence of withdrawal syndrome in patients with myelofibrosis [ Time Frame: Up to 1 year ]

Other Outcome Measures:
  1. Immune recovery and cytokines [ Time Frame: Up to 1 year ]
    Generalized linear mixed models will be used to assess the association between cytokines over time and treatment and other factors.

  2. Deoxyribonucleic acid (DNA) damage studies [ Time Frame: Up to 1 year ]
    The proportion of patients with DNA damage will be reported, and generalized logistic mixed models may be used to assess the association with similar covariates.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04127721


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Uday R Popat M.D. Anderson Cancer Center
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04127721    
Other Study ID Numbers: 2018-0505
NCI-2019-05753 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2018-0505 ( Other Identifier: M D Anderson Cancer Center )
First Posted: October 16, 2019    Key Record Dates
Last Update Posted: October 29, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hematologic Diseases
Graft vs Host Disease
Immune System Diseases
Methotrexate
Fludarabine
Busulfan
Tacrolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Calcineurin Inhibitors
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists