Clinical Trial: Ruxolitinib Phosphate and Chemotherapy Given Before and After Reduced Intensity Donor Stem Cell Transplant in Treating Patients With Myelofibrosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Pilot Open-Label Study of Safety and Efficacy of Ruxolitinib Given Peri-transplant During Reduced Intensity Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients With M

Brief Summary: This pilot clinical trial studies the side effects and best dose of ruxolitinib phosphate when given together with chemotherapy before and after a donor stem cell transplant in treating patients with myelofibrosis. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine phosphate and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ruxolitinib phosphate together with chemotherapy before and after a donor stem cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Among the dose levels tested, to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of ruxolitinib phosphate (ruxolitinib), when given as part of reduced intensity allogeneic hematopoietic cell transplant (HCT), in patients with myelofibrosis.

II. To determine if the addition of ruxolitinib is safe by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.

SECONDARY OBJECTIVES:

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

II. To estimate the cumulative incidence of acute graft-versus-host disease (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 estimate the probabilities of overall and progression-free survival (OS/PFS) at 1- and 2-years post transplant.

V. To characterize changes in aGVHD biomarkers (Reg-3 alpha, soluble tumor necrosis factor receptor I [sTNF RI], IL2R alpha), janus associated kinases (JAK)-regulated pro-inflammatory cytokines (i.e. IL-6, TNF alpha, CRP, beta 2microglobulin) and 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 phosph
Sponsor: City of Hope Medical Center

Current Primary Outcome: MTD of ruxolitinib phosphate, defined as less than or equal to 1 of 6 dose limiting toxicities, graded according to the Bearman criteria and the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 45 days post stem cell infusion ]

Original Primary Outcome: MTD of ruxolitinib phosphate, defined as less than or equal to 1 of 6 dose limiting toxicities, graded according to the Bearman criteria and the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 60 days post stem cell infusion ]

Current Secondary Outcome:

• Cumulative incidence of aGVHD, graded and staged according to the Consensus Grading [ Time Frame: Up to 100 days post stem cell infusion ]
  Will be calculated using the Gray method with prior death or relapse considered competing events.
• Cumulative incidence of chronic GVHD, graded and staged according to the Consensus Grading [ Time Frame: Up to 100 days post stem cell infusion ]
  Will be calculated using the Gray method with prior death or relapse considered competing events.
• Cumulative incidence of relapse/progression [ Time Frame: Up to 2 years ]
  Will be calculated as a competing risk using the Gray method.
• Engraftment (recovery of granulopoiesis and megakaryopoiesis) [ Time Frame: Up to 100 days post stem cell infusion ]
  Defined as absolute neutrophil count >= 0.5 x 10^3/ul sustained for 3 consecutive lab values on different days with no subsequent decline, and platelets >= 20 K/ul independent of platelet transfusion support.
• Incidence of infections [ Time Frame: Up to 100 days post stem cell infusion ]
  Will be reported by site of disease, date of onset, severity and resolution, if any.
• NRM, defined as death occurring in a patient from causes other than relapse or progression [ Time Frame: Up to 2 years ]
  Will be calculated as a competing risk using the Gray method.
• OS [ Time Frame: From the day of stem cell infusion until death, or last follow-up, whichever occurs first, assessed for up to 2 years ]
  Will be calculated using the Kaplan-Meier method.
• PFS [ Time Frame: From the day of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, whichever occurs first, assessed for up to 2 years ]
  Will be calculated using the Kaplan-Meier method.

Original Secondary Outcome: Same as current

Information By: City of Hope Medical Center

Dates:
Date Received: September 26, 2016
Date Started: October 5, 2016
Date Completion: October 2019
Last Updated: March 9, 2017
Last Verified: March 2017