Ruxolitinib Prior to Transplant in Patients With Myelofibrosis

NCT01790295 | Terminated Phase 2 Results DMC

• 2 other identifiers: GCO 12-1809MPD-RC 114
• Study Type: interventional
• Target: 21
• Locations: 3 countries
• Sites: 8

Brief Summary

The purpose of this study is to find out if giving the study drug Ruxolitinib (INC424) prior to a combination of other chemotherapeutic drugs (Fludarabine and Busulfan) before infusing another person's hematopoietic stem cells (bone marrow transplantation) will be successful in people who have advanced primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF), collectively known as myelofibrosis (MF). MF is a disorder in which bone marrow tissue develops in abnormal sites because the bone marrow itself undergoes fibrosis or scarring. This study plans to evaluate whether adding the drug Ruxolitinib will further aid in reducing pre-transplant spleen size, improve physical performance levels and reduce adverse events (side effects) related to the transplant. Ruxolitinib is a drug that is approved by the FDA for the treatment of patients with advanced forms of myelofibrosis. Using Ruxolitinib prior to stem cell transplantation is experimental.

Conditions

Primary Myelofibrosis; Post Polycythemia Vera Myelofibrosis; Post Essential Thrombocythemia Myelofibrosis

Keywords

Myelofibrosis; Stem cell transplant; Ruxolitinib

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With 100-day Survival Without Graft Failure

  The feasibility of combining Ruxolitinib (INC424) with a Reduced intensity conditioning (RIC) regimen likely to produce success post transplantation, success being defined as patient being alive, and without graft failure at day 100-post allogeneic stem cell transplantation (in patients who receive (a) related donor transplant and in those who receive (b) an unrelated donor transplant.

  Day 100-post allogeneic stem cell transplantation

Secondary Outcomes (19)

• Time to Neutrophil Recovery

  up to 4 years

• Platelet Recovery

  up to 4 years

• Percent of Participants With Non-relapse Mortality (NRM)

  100 days

• Percent of Participants With Non-relapse Mortality (NRM)

  1-year post transplant

• Percent of Participants With Graft Versus Host Disease (GvHD)

  1-year post transplant

Study Arms (1)

Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)

EXPERIMENTAL

Ruxolitinib (INC424) tablets will be started 62 days (day -67) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib will be determined according to baseline platelet count and will be modified according to platelet count at follow-up. The drug will be given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and will be stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug will be supplied as 5 mg tablets.

Drug: Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)

Interventions

Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) DRUG

Ruxolitinib (INC424) tablets will be started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib will be determined according to baseline platelet count and will be modified according to platelet count at follow-up. The drug will be given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and will be stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug will be supplied as 5 mg tablets.

Also known as: Ruxolitinib \Pre- Hematopoietic cell transplantation (HCT), INC424

Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented diagnosis of primary myelofibrosis according to WHO criteria or post PV myelofibrosis or post ET myelofibrosis as per IWG-MRT criteria
• Age 18-70 years
• Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria OR Intermediate-1 risk disease with one of the following additional unfavorable features known to impact the survival adversely
• Red cell transfusion dependency
• Unfavorable Karyotype
• Platelet count \<100 x 109/l
• Blasts in the PB and BM ≤10% prior to study enrollment
• Availability of a suitable matched related (6/6 or 5/6) or unrelated donor (10/10 or 9/10 antigen or allele matched).
• Able to give informed written consent
• ECOG Performance status of 0-2.
• Life expectancy \>3 months
• Off all MF-directed therapy including investigational agents for at least 2 weeks prior to study enrollment and recovered from all toxicities\*
• Adequate organ function
• Adequate renal function - creatinine \<1.5 x IULN
• Adequate hepatic function - AST/ALT \<2.5 x IULN, Total Bilirubin \<1.5 x IULN

You may not qualify if:

• Any previous JAK2 inhibitor treatment prior to study enrollment, with the exception of Ruxolitinib
• Hypersensitivity to JAK inhibitor
• Clinical or laboratory evidence of cirrhosis
• Prior allogeneic transplant for any hematopoietic disorder
• \>20% blast in the PB or BM prior to HCT or had leukemic transformation (\>20% blasts in PB or BM any time prior to HCT)
• Syngeneic donor
• Cord Blood transplant
• Active uncontrolled infection
• H/o another malignancy within 5-years of date of HCT except h/o basal cell or squamous cell carcinoma of skin or PV or ET
• Known HIV positive
• Pregnancy at the time of BMT
• Any other concurrent illness which in investigator's opinion puts the patient at excessive risk of treatment related toxicities
• Unable to give informed consent
• Active infection with hepatitis A,B or C virus
• Subjects who require therapy with a strong CYP3A4 inhibitor prior to enrollment to this study

Sponsors & Collaborators

• John Mascarenhas: lead
• Myeloproliferative Disorders-Research Consortium: collaborator
• National Cancer Institute (NCI): collaborator
• Incyte Corporation: collaborator
• Novartis: collaborator

Study Sites (8)

Emory Hospital

Atlanta, Georgia, 30322, United States

Location

Northwestern University, Robert h. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Princess Margaret Cancer Centre, University of Toronto

Toronto, M5G 2M9, Canada

Location

University of Oxford

Oxford, OX3 9DS, United Kingdom

Location

Related Publications (1)

• Gupta V, Kosiorek HE, Mead A, Klisovic RB, Galvin JP, Berenzon D, Yacoub A, Viswabandya A, Mesa RA, Goldberg J, Price L, Salama ME, Weinberg RS, Rampal R, Farnoud N, Dueck AC, Mascarenhas JO, Hoffman R. Ruxolitinib Therapy Followed by Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation for Myelofibrosis: Myeloproliferative Disorders Research Consortium 114 Study. Biol Blood Marrow Transplant. 2019 Feb;25(2):256-264. doi: 10.1016/j.bbmt.2018.09.001. Epub 2018 Sep 8.

  PMID: 30205231 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr. John Mascarenhas
• Organization: Icahn School of Medicine at Mount Sinai

john.mascarenhas@mssm.edu

212-241-3417

Study Officials

• John Mascarenhas, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Vikas Gupta, MD, FRCP, FRCPath

  University of Toronto

  STUDY CHAIR

• Adam Mead, MD

  University of Oxford, John Radcliffe Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 8, 2013
• First Posted: February 13, 2013
• Study Start: November 1, 2013
• Primary Completion: October 26, 2017
• Study Completion: October 26, 2017
• Last Updated: March 20, 2019
• Results First Posted: March 20, 2019

Record last verified: 2019-02

Locations

CA (1); GB (1); US (6)