PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis

April 3, 2019 updated by: Ivan S Moiseev, St. Petersburg State Pavlov Medical University

Graft-versus-host Disease Prophylaxis With Post-transplantation Cyclophosphamide and Ruxolitinib in Patients With Myelofibrosis

A number of groups have demonstrated very low incidence of acute and chronic graft-versus-host disease (GVHD) with post-transplantation cyclophosphamide (PTCy) in haploidentical and unrelated allogeneic stem cell transplantation (SCT). Still the relapse of the underlining malignancy is a problem after this prophylaxis. Ruxolitinib is currently one of the most promising drugs in the treatment of steroid-refractory GVHD. On the other hand, its primary indication is myelofibrosis, and it was demonstrated that ruxolitinib before allogeneic SCT might improve the outcome. This pilot trial evaluates whether the combination of PTCy and ruxolitinib facilitates adequate GVHD control, and decreases the risk of graft failure and disease progression in myelofibrosis patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Saint-Petersburg, Russian Federation, 197089
        • First Pavlov State Medical University of St. Petersburg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have an indication for allogeneic hematopoietic stem cell transplantation
  • Diagnosis:

Primary myelofibrosis Secondary myelofibrosis

  • Signed informed consent
  • Matched related, 8-10/10 HLA-matched unrelated or haploidentical donor available. The HLA typing is performed by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
  • No second tumors
  • No severe concurrent illness

Exclusion Criteria:

  • Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
  • Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
  • Respiratory distress >grade I
  • Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
  • Creatinine clearance < 60 mL/min
  • Uncontrolled bacterial or fungal infection at the time of enrollment
  • Requirement for vasopressor support at the time of enrollment
  • Karnofsky index <30%
  • Pregnancy
  • Somatic or psychiatric disorder making the patient unable to sign informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PTCy and ruxolitinib
Procedure: Allogeneic hematopoietic stem cell transplantation
Day 0: Infusion of unmanipulated graft
Other Names:
  • HSCT
Drug: Busulfan
Days -5 through -3: Busulfan 1 mg/kg po qid №10
Drug: Fludarabine monophosphate
Days -7 through -2: 30 mg/m2/day iv qd x 6 days
Drug: Cyclophosphamide
Day +3 and +4: 50 mg/kg/day iv qd
Other Names:
  • Cytoxan
Drug: Ruxolitinib
Days -8 through -2 15 mg tid
Drug: Ruxolitinib
Days +5 through +100: 7.5 mg bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of chronic GVHD, moderate and severe (NIH criteria)
Time Frame: 365 days
365 days
Incidence of acute graft-versus-host disease, grades II-IV
Time Frame: 180 days
180 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
Time Frame: 100 days
100 days
Incidence of primary or secondary graft failure
Time Frame: 60 days
60 days
Non-relapse mortality analysis
Time Frame: 365 days
Non-relapse mortality is defined as any death in absence of relapse or progressive disease. Summarized using Kaplan-Meier and cumulative incidence estimates.
365 days
Overall survival analysis
Time Frame: 365 days
Summarized using Kaplan-Meier and cumulative incidence estimates.
365 days
Event-free survival analysis
Time Frame: 365 days
Event is defined as relapse or death in the specified time frame. Summarized using Kaplan-Meier and cumulative incidence estimates.
365 days
Relapse rate analysis
Time Frame: 365 days
Summarized using Kaplan-Meier and cumulative incidence estimates.
365 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time Frame: 100 days
Toxicity parameters based on NCI CTCAE 4.03 grades: hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), mucositis (attending physician assessment), hemorrhagic cystitis (attending physician assessment), cardiotoxicity (ECG, echocardiography). Additional toxicity parameters: incidence and severity of veno-occlusive disease, incidence of transplant-associated microangiopathy
100 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Petersburg State Pavlov Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2016

Primary Completion (Actual)

December 1, 2018

Study Completion (Actual)

April 1, 2019

Study Registration Dates

First Submitted

June 8, 2016

First Submitted That Met QC Criteria

June 15, 2016

First Posted (Estimate)

June 20, 2016

Study Record Updates

Last Update Posted (Actual)

April 4, 2019

Last Update Submitted That Met QC Criteria

April 3, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 04/16-n

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Consultations with lawyers are ongoing about how IPD initiative fits the local law "About personal data 152-fz".

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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