PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis

Phase 1

Completed

• Conditions: Primary Myelofibrosis; Myeloproliferative Disorders
• Interventions: Procedure: Allogeneic hematopoietic stem cell transplantation; Drug: Busulfan; Drug: Fludarabine monophosphate; Drug: Cyclophosphamide; Drug: Ruxolitinib

• Registration Number: NCT02806375
• Lead Sponsor: St. Petersburg State Pavlov Medical University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-06-08
• Study First Submitted QC: 2016-06-15
• Study First Posted: 2016-06-20
• Primary Completion: 2018-12
• Status Verified: 2019-04
• Study Completion: 2019-04
• Last Update Submitted: 2019-04-03
• Last Update Posted: 2019-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PTCy and ruxolitinib	Fludarabine monophosphate	-
PTCy and ruxolitinib	Allogeneic hematopoietic stem cell transplantation	-
PTCy and ruxolitinib	Busulfan	-
PTCy and ruxolitinib	Cyclophosphamide	-
PTCy and ruxolitinib	Ruxolitinib	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Incidence of primary or secondary graft failure	60 days
Event-free survival analysis	365 days	Event is defined as relapse or death in the specified time frame. Summarized using Kaplan-Meier and cumulative incidence estimates.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	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
Non-relapse mortality analysis	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.
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence	100 days
Overall survival analysis	365 days	Summarized using Kaplan-Meier and cumulative incidence estimates.
Relapse rate analysis	365 days	Summarized using Kaplan-Meier and cumulative incidence estimates.

Trial Locations

Locations (1)

First Pavlov State Medical University of St. Petersburg; 🇷🇺 Saint-Petersburg, Russian Federation