Non Hodgkin Lymphoma Clinical Trial

Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation

Summary

In this trial, the investigators will begin to explore the possibility that, as in mice, janus kinase inhibitor 1 (JAK1) inhibition with haploidentical-hematopoietic cell transplantation (HCT) may mitigate graft-versus-host-disease (GVHD) and cytokine release syndrome (CRS) while retaining Graft-versus-Leukemia (GVL) and improving engraftment. The purpose of this pilot study is to determine the safety of itacitinib with haplo-hematopoietic cell transplantation (HCT) measured by the effect on engraftment and grade III-IV GVHD.

View Eligibility Criteria

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 (based on International Working Group (IWG) Criteria)
Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD negative, based on IWG Criteria)
Myelodysplastic syndrome with ≤ 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, including (but not limited to) sibling, offspring, cousin, nephew, or parent. Younger donors should be prioritized.
At least 18 years of age
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 cells (HSC).
No active hepatitis.
Negative for human T-cell lymphotrophic virus (HTLV) and human immunodeficiency virus (HIV).
Not pregnant.
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

Adequate organ function as defined below:

Total bilirubin must be within normal range at baseline
Aspartate aminotransferase (AST)(SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3.0 x institutional upper limit of normal (IULN).
Creatinine ≤ 1.5 x IULN OR creatinine clearance ≥ 45 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 (FEV1) and forced vital capacity (FVC) ≥ 40% predicted, diffusing 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.
At least 18 years of age at the time of study registration
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 antibodies (DSA) with Mean Fluorescence Intensity (MFI) of ≥2000 as assessed by the single antigen bead assay.
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 (unless they are enrolled Amendment #5 or later) 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.

Additional Inclusion Criteria Under Amendment 5

Five subjects with myelofibrosis will be enrolled in the expansion phase.
Three patients whose donors fail to collect the target number of CD34+ cells and the treating physician choses to move forward with the haplo-HCT will be enrolled in the expansion phase.

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

55

Study ID:

NCT03755414

Recruitment Status:

Active, not recruiting

Sponsor:

Washington University School of Medicine

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There is 1 Location for this study

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Washington University School of Medicine
Saint Louis Missouri, 63110, United States

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

55

Study ID:

NCT03755414

Recruitment Status:

Active, not recruiting

Sponsor:


Washington University School of Medicine

How clear is this clinincal trial information?

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