Adding Itacitinib to Cyclophosphamide and Tacrolimus for the Prevention of Graft Versus Host Disease in Patients Undergoing Hematopoietic Stem Cell Transplants

Acute Myeloid Leukemia Clinical Trial

Official title: Single Center Pilot Study to Investigate the Efficacy of Adding Itacitinib to Post-Transplant Cyclophosphamide as Graft-Versus-Host Disease Prophylaxis After Reduced Intensity Conditioning Matched Donor Hematopoietic Cell Transplantation With Peripheral Blood Stem Cells as Graft Source

Status Recruiting

Clinical Trial Summary

This clinical trial evaluates the safety and effectiveness of adding itacitinib to cyclophosphamide and tacrolimus for the prevention of graft versus host disease (GVHD) in patients undergoing hematopoietic stem cell transplant. Itacitinib is an enzyme inhibitor that may regulate the development, proliferation, and activation of immune cells important for GVHD development. Cyclophosphamide and tacrolimus are immunosuppressive agents that may prevent GVHD in patients who receive stem cell transplants. Giving itacitinib in addition to cyclophosphamide and tacrolimus may be more effective at preventing GVHD in patients receiving hematopoietic stem cell transplants.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Safety lead-in: Determine if shortening tacrolimus administration period to 60 days (day +65 post-hematopoietic cell transplantation [HCT]), when combined with post-transplant cyclophosphamide (PTCy) and itacitinib at a fixed dose level as graft-versus-host disease (GVHD) prophylaxis, is safe and effective after mobilized peripheral blood stem cell (PBSC) allogeneic hematopoietic cell transplantation (HCT) from a matched related/unrelated donor, as assessed by grade 3-4 GVHD as dose limiting toxicity.

II. Following the safety lead-in, evaluate the efficacy of PTCy, itacitinib and tacrolimus GVHD prophylaxis, as assessed by 1-year GVHD-free relapse-free survival (GRFS).

SECONDARY OBJECTIVES:

I. Evaluate the safety of this regimen by assessing:

Ia. Adverse events: type, frequency, severity, attribution, time course, duration.

Ib. Complications including acute and chronic GVHD, infections and delayed engraftment.

II. Estimate overall survival (OS), progression-free survival (PFS), cumulative incidences of relapse/disease progression, and non-relapse mortality (NRM) at 100 days, and 1-year post-transplant.

III. Estimate rates of acute and chronic GvHD, infections, and neutrophil recovery.

EXPLORATORY OBJECTIVES:

I. Donor cell engraftment will be assessed by count monitoring and short tandem repeat (STR) chimerism analysis on days +30 and day +100.

II. Describe the kinetics of immune cell recovery. III. Evaluate patient's quality of life on day +100, 6 months and one-year post-HCT.

IV. Pharmacokinetics: serial blood sampling will be done to evaluate the steady-state pharmacokinetics of itacitinib after PTCy.

V. Describe the kinetics of GVHD biomarkers, JAK-related inflammatory cytokines and STAT phosphorylation.

VI. Evaluate and describe the cytokine release syndrome (CRS) post-HCT by assessing the incidence, frequency, and severity of CRS.

VII. Obtain a preliminary estimate of gut microbiome diversity at baseline (preferably before fludarabine administration), and then on days +14, +30, and +100.

OUTLINE:

Patients undergo peripheral blood stem cell infusion on day 0. Patients receive cyclophosphamide intravenously (IV) once daily (QD) on days 3 and 4, itacitinib orally (PO) QD on days 5-100, and tacrolimus IV or PO on days 6-65.

After completion of study treatment, patients are followed up at day 180 and 1 year. ;

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Chronic Myelomonocytic Leukemia
• Graft vs Host Disease
• Leukemia
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Primary Myelofibrosis
• Secondary Myelofibrosis

• NCT number: NCT05364762
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Recruiting
• Phase: Phase 2
• Start date: November 23, 2022
• Completion date: April 28, 2024