Skip to main content
OpenTrials
Completed

NCT Number: NCT02806375

PTCy and Ruxolitinib GVHD Prophylaxis in 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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Primary Myelofibrosis Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Myeloproliferative Disorders

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, 197089, Russia

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

allogeneic hematopoietic stem cell transplantation

Procedure

Day 0: Infusion of unmanipulated graft

Other names: HSCT

busulfan

Drug

Days -5 through -3: Busulfan 1 mg/kg po qid №10

Fludarabine monophosphate

Drug

Days -7 through -2: 30 mg/m2/day iv qd x 6 days

Cyclophosphamide

Drug

Day +3 and +4: 50 mg/kg/day iv qd

Other names: Cytoxan

Ruxolitinib

Drug

Days -8 through -2 15 mg tid

Primary outcomes

  1. Incidence of acute graft-versus-host disease, grades II-IV

    Time frame: 180 days

  2. Incidence of chronic GVHD, moderate and severe (NIH criteria)

    Time frame: 365 days

Secondary outcomes

  1. Incidence of primary or secondary graft failure

    Time frame: 60 days

  2. 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.

  3. Overall survival analysis

    Time frame: 365 days

    Summarized using Kaplan-Meier and cumulative incidence estimates.

  4. 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.

  5. Relapse rate analysis

    Time frame: 365 days

    Summarized using Kaplan-Meier and cumulative incidence estimates.

  6. 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

  7. Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

    Time frame: 100 days

Sponsors and collaborators

Lead sponsor

St. Petersburg State Pavlov Medical University

Other

Registry information

Official study title

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

Important dates

Study start
2016
Primary completion
2018
Study completion
2019
First posted
Jun 20, 2016
Registry last updated
Apr 4, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.