NCT02528877

Ruxolitinib Phosphate, Tacrolimus and Sirolimus in Preventing Acute Graft-versus-Host Disease During Reduced Intensity Donor Hematopoietic Cell Transplant in Patients With Myelofibrosis

A Phase I Trial of Ruxolitinib Combined With Tacrolimus and Sirolimus as Acute Graft-versus-Host Disease (aGVHD) Prophylaxis During Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of ruxolitinib phosphate when given together with tacrolimus and sirolimus in preventing acute graft-versus-host disease during reduced intensity donor hematopoietic cell transplant in patients with myelofibrosis. Sometimes transplanted cells from a donor can attack the normal tissue of the transplant patient called graft-versus-host disease. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It may also reduce graft-versus-host disease by reducing inflammation and immune modulation. Giving ruxolitinib phosphate together with tacrolimus and sirolimus after transplant may prevent graft-versus-host disease.

Detailed description

PRIMARY OBJECTIVES: I. Among the dose levels tested, to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of ruxolitinib (ruxolitinib phosphate), when given in combination with tacrolimus and sirolimus (TAC/SIR) as acute graft-versus-host disease (aGVHD) prophylaxis as part of reduced intensity allogeneic hematopoietic cell transplant (HCT), in patients with myelofibrosis or other related myeloid neoplasm with marrow fibrosis. SECONDARY OBJECTIVES: I. To determine if the addition of ruxolitinib, to the standard aGVHD prophylactic regimen of TAC/SIR, is safe by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. II. To estimate the cumulative incidence of aGVHD and non-relapse mortality (NRM) at 100-days post transplant. III. To estimate the cumulative incidence of chronic GVHD at 1- and 2-years post transplant. IV. To characterize and evaluate hematologic recovery, donor cell engraftment and immune reconstitution by cell count and flow cytometry of lymphocyte subsets. V. To estimate the probabilities of overall and progression-free survival (OS/PFS) at 1- and 2-years post transplant. VI. To characterize changes in aGVHD biomarkers (regenerating islet-derived 3-alpha \[Reg-3alpha\], soluble tumor necrosis factor receptor I \[sTNF RI\], interleukin 2 receptor alpha \[IL2Ralpha\]), Janus-associated kinase (JAK)-regulated pro-inflammatory cytokines (i.e. interleukin \[IL\]-6, tumor necrosis factor \[TNF\] alpha, C-reactive protein \[CRP\], beta 2 microglobulin) and signal transducer and activator of transcription 3 (STAT3) phosphorylation (downstream of JAK signaling) over time and by aGVHD status/grade. OUTLINE: This is a dose-escalation study of ruxolitinib phosphate. PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -9 to -5 and melphalan IV over 20 minutes on day -4. Beginning greater than 48 hours after completion of melphalan, patients undergo peripheral blood stem cell or bone marrow transplant according to standard guidelines on day 0. GVHD PROPHYLAXIS: Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days -3 to 30 tapered to day 60, tacrolimus IV continuously or PO BID on days -3 to 100 , and sirolimus PO once daily (QD) on day -3 to 100. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up 2 years.

Conditions

• Acute Myeloid Leukemia in Remission
• Primary Myelofibrosis
• Primary Myelofibrosis, Prefibrotic Stage
• Secondary Acute Myeloid Leukemia
• Secondary Myelofibrosis

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Bone Marrow Transplantation	Undergo allogeneic bone marrow transplant
PROCEDURE	Allogeneic Hematopoietic Stem Cell Transplantation	Undergo allogeneic hematopoeitic stem cell transplant
DRUG	Fludarabine Phosphate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Melphalan	Given IV
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo hematopoietic stem cell transplant
OTHER	Pharmacological Study	Correlative studies
DRUG	Ruxolitinib Phosphate	Given PO
DRUG	Sirolimus	Given PO
DRUG	Tacrolimus	Given IV or PO

Timeline

• Start date: 2015-11-01
• Primary completion: 2016-09-01
• First posted: 2015-08-19
• Last updated: 2016-09-14

Locations

1 site across 1 country: United States