Clinical Trials Logo

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. ;


Study Design


Related Conditions & MeSH terms


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

See also
  Status Clinical Trial Phase
Completed NCT04022785 - PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Phase 1
Completed NCT01200355 - Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome Phase 4
Active, not recruiting NCT02530463 - Nivolumab and/or Ipilimumab With or Without Azacitidine in Treating Patients With Myelodysplastic Syndrome Phase 2
Completed NCT02057185 - Occupational Status and Hematological Disease
Completed NCT01682226 - Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies Phase 2
Completed NCT02485535 - Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant Phase 1
Completed NCT03941769 - 2018-0674 - IL-7 for T-Cell Recovery Post Haplo and CB Transplant - Phase I/II Phase 1/Phase 2
Completed NCT00001637 - Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults Phase 2
Recruiting NCT06195891 - Orca-T Following Chemotherapy and Total Marrow and Lymphoid Irradiation for the Treatment of Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia or Myelodysplastic Syndrome Phase 1
Active, not recruiting NCT04188678 - Resiliency in Older Adults Undergoing Bone Marrow Transplant N/A
Completed NCT00987480 - Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine Phase 2
Recruiting NCT02356159 - Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation Phase 1/Phase 2
Completed NCT04666025 - SARS-CoV-2 Donor-Recipient Immunity Transfer
Completed NCT02756572 - Early Allogeneic Hematopoietic Cell Transplantation in Treating Patients With Relapsed or Refractory High-Grade Myeloid Neoplasms Phase 2
Terminated NCT02877082 - Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients Phase 2
Completed NCT02543879 - Study of a Novel BET Inhibitor FT-1101 in Patients With Relapsed or Refractory Hematologic Malignancies Phase 1
Completed NCT02262312 - Iron Overload and Transient Elastography in Patients With Myelodysplastic Syndrome Phase 0
Completed NCT02188290 - Transplant-Related Mortality in Patients Undergoing a Peripheral Blood Stem Cell Transplantation or an Umbilical Cord Blood Transplantation N/A
Recruiting NCT02330692 - Cohort Study of New Prognostic Factors With Peripheral Blood and Bone Marrow Evaluation at the Time of Diagnosis and Relapse in Myelodysplastic Syndrome
Completed NCT01684150 - A Phase 1, Open-Label, Dose-Escalation & Expanded Cohort, Continuous IV Infusion, Multi-center Study of the Safety, Tolerability,PK & PD of EPZ-5676 in Treatment Relapsed/Refractory Patients With Leukemias Involving Phase 1