Itacitinib in Reducing the Incidence of Graft Versus Host Disease in Patients with Hematologic Cancers Undergoing Donor Stem Cell Transplant

Status: Active

Description

This phase I trial studies the side effects of itacitinib in reducing the incidence of graft versus host disease (GVHD) in patients with hematologic (bone marrow and blood cells) cancers undergoing donor stem cell transplant. One of the side effects of a donor stem cell transplant is the development of GVHD, which occurs when some of the cells from the donor attack the recipient’s tissues, resulting in mild, moderate, or even life-threatening side effects to the recipient’s skin, stomach, intestine, and liver. Itacitinib may prevent or lessen the effect of GVHD while still effectively treating the hematologic cancer.

Eligibility Criteria

Inclusion Criteria

  • Patients must meet the following criteria within 30 days prior to day 0 unless otherwise noted
  • Diagnosis of a hematological malignancy listed below: * Acute myelogenous leukemia (AML) in complete morphological remission (minimal residual disease [MRD] negative, based on International Working Group [IWG] criteria) * Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD negative, based on IWG Criteria) * Myelodysplastic syndrome with less than 5% blasts in bone marrow * Non-Hodgkin’s lymphoma (NHL) or Hodgkin’s disease (HD) in 2nd or greater complete or partial remission
  • Planned treatment is myeloablative or reduced intensity conditioning followed by T Cell–replete peripheral blood haploidentical donor transplantation
  • Available human leukocyte antigen (HLA)-haploidentical donor who meets the following criteria: * Blood-related family member who is either a sibling (full or half) or offspring ** Other donors will be excluded, including: parent, cousin, niece or nephew, aunt or uncle, and grandparent * HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards * In the investigator’s opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting hematopoietic stem cell (HSC) * No active hepatitis * Negative for human T-cell lymphotropic virus (HTLV) and human immunodeficiency virus (HIV) * Not pregnant * Donor selection will be in compliance with Food and Drug Administration (FDA) guidelines as provided in 21 CFR 1271 for donor eligibility * Safety lead-in phase: for the first three patients, the donor must consent to a second product collection should it prove necessary
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Total bilirubin must be within normal range at baseline
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional upper limit of normal (IULN)
  • Estimated creatinine clearance >= 60 mL/min/1.73 m^2 by Cockcroft-Gault formula
  • Oxygen saturation >= 90% on room air
  • Left ventricular ejection fraction (LVEF) >= 40%
  • Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) >= 40% predicted, corrected diffusion capacity of the lung for carbon monoxide (DLCOc) >= 40% predicted. If DLCO is < 40%, patients will still be considered eligible if deemed safe after a pulmonary evaluation
  • Able to understand and willing to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)
  • Must be able to receive GVHD prophylaxis with tacrolimus, mycophenolate mofetil, and cyclophosphamide

Exclusion Criteria

  • Must not have undergone a prior allogeneic donor (related, unrelated, or cord) transplant. Prior autologous transplant is not exclusionary
  • Presence of donor-specific anti-HLA antibodies
  • Known HIV or active hepatitis B or C infection
  • Known hypersensitivity to one or more of the study agents, including ruxolitinib and itacitinib
  • Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 35 days after transplant
  • Must not receive antithymocyte globulin as part of pre-transplant conditioning regimens
  • Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug (day -3)
  • Pregnant and/or breastfeeding
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements
  • Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency will not be excluded

Locations & Contacts

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Contact: Mark Andrew Schroeder
Phone: 314-454-8304
Email: markschroeder@wustl.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the cumulative incidence of graft failure at 35 days post haploidentical (haplo)-hematopoietic cell transplantation (HCT).

II. To determine the cumulative incidence of grade III-IV acute GVHD by day 100.

SECONDARY OBJECTIVES:

I. To determine the incidence and grade of cytokine release syndrome (CRS).

II. To determine treatment related mortality at day 180.

EXPLORATORY OBJECTIVES:

I. Cumulative incidence of relapse at six months and one year.

II. Overall survival at 6 months and one year.

III. To determine the cumulative incidence of failure of platelet engraftment 35 days post haplo-HCT.

IV. GVHD relapse free survival (GRFS) at one year.

V. Incidence and types of infections within one year.

VI. Cumulative incidence of acute GVHD grade II-IV at day 180.

VII. Cumulative incidence of acute GVHD grades III-IV at day 180.

VIII. Cumulative incidence of chronic GVHD at one year post transplant.

IX. Incidence of IL-6 inhibitor therapy.

X. Will collect annotated patient samples for analysis of cytokines, JAK/STAT phosphorylation, and immune reconstitution and look for associations with patient outcomes.

OUTLINE:

Patients receive itacitinib orally (PO) once daily (QD) on days -3 to 100 and tapered up to day 160. Patients also receive standard of care conditioning regimens prior to undergoing haplo-HCT on day 0, as well as standard of care GVHD prophylaxis comprising cyclophosphamide on days 3 and 4, tacrolimus PO or intravenously (IV) on days 5 to 100 before tapering, and mycophenolate mofetil PO or IV thrice daily (TID) on days 5 to 35. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Mark Andrew Schroeder

Trial IDs

Primary ID 201903114
Secondary IDs NCI-2019-03174
Clinicaltrials.gov ID NCT03755414