Itacitinib, Tacrolimus, and Sirolimus for the Prevention of GVHD in Patients With Acute Leukemia, Myelodysplastic Syndrome, or Myelofibrosis Undergoing Reduced Intensity Conditioning Donor Stem Cell Transplantation

Myelodysplastic Syndrome Clinical Trial

Official title: Phase IIa Study of Addition of Itacitinib With Tacrolimus/Sirolimus Regimen for GVHD Prophylaxis in Fludarabine and Melphalan Non-Myeloablative Conditioning Hematopoietic Cell Transplantation for Acute Leukemias, MDS or MF

Status Active, not recruiting

Clinical Trial Summary

This phase IIa trial studies the side effects of itacitinib when given together with standard treatment (tacrolimus and sirolimus), and to see how well it works in preventing graft-versus-host-disease (GVHD) in patients with acute leukemia, myelodysplastic syndrome or myelofibrosis who are undergoing reduced intensity conditioning donor stem cell transplantation. GVHD is a common complication after donor stem cell transplantation, resulting from donor immune cells recognizing recipients' cells and attacking them. Adding itacitinib to tacrolimus and sirolimus may reduce the risk GVHD and ultimately improve overall outcome and survival after donor stem cell transplantation.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. Following a patient safety lead-in, estimate graft-versus-host disease free relapse free (GRFS) survival at 1- year post allogeneic stem cell transplantation (alloHCT).

SECONDARY OBJECTIVES:

I. Estimate the cumulative incidence of acute graft-versus-host disease (aGVHD) and non-relapse mortality (NRM) at 100-days post-transplant.

II. Estimate the cumulative incidence of chronic GVHD at 1- and 2-years post-transplant.

III. Estimate the probabilities of overall and progression-free survival (OS/PFS) at 1- and 2-years post-transplant.

IV. Estimate rate of infection and development of second malignancies including lymphoproliferative disorders at 1- and 2-years post-transplant.

V. Assess patients' quality of life (QOL) at day 100 and 1 year post alloHCT.

EXPLORATORY OBJECTIVES:

I. Characterize and evaluate hematologic recovery, donor cell engraftment and immune reconstitution by cell count and flow cytometry of lymphocyte subsets.

II. Characterize changes in aGVHD biomarkers (Reg-3alpha, TNF-RI, and ST2) and a composite biomarker panel (IL2Ralpha, TNF-R1, IL-8, and hepatocyte growth factor), JAK-regulated pro-inflammatory cytokines (i.e., IL-6, TNFalpha, CRP, Beta2 Microglobulin, and IFNgamma) and STAT3 phosphorylation (downstream of JAK signaling) over time and by aGVHD status/grade.

OUTLINE:

REDUCED INTENSITY CONDITIONING (RIC): Patients receive fludarabine via infusion on days -9 to -5 and melphalan on day -4 in the absence of disease progression or unacceptable toxicity.

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT): Patients undergo HSCT on day 0.

GVHD PROPHYLAXIS: Patients receive itacitinib orally (PO) once daily (QD) beginning on day -3 and continuing until day 100 in the absence of disease progression or unacceptable toxicity. Patients also receive tacrolimus intravenously (IV) or PO and sirolimus PO beginning day -3 and continuing until day 100 with a taper in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then periodically for up to 2 years post- transplantation. ;

Related Conditions & MeSH terms

• Acute Disease
• Acute Leukemia
• Hematologic and Lymphocytic Disorder
• Hematologic Diseases
• Leukemia
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Primary Myelofibrosis
• Secondary Myelofibrosis
• Syndrome

• NCT number: NCT04339101
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 11, 2020
• Completion date: May 22, 2024