PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis

St. Petersburg State Pavlov Medical University

Status and phase

Completed

Phase 2

Phase 1

Conditions

Primary Myelofibrosis

Myeloproliferative Disorders

Treatments

Drug: Fludarabine monophosphate

Drug: Cyclophosphamide

Drug: Ruxolitinib

Procedure: Allogeneic hematopoietic stem cell transplantation

Drug: Busulfan

Study type

Interventional

Funder types

Other

Identifiers

NCT02806375

04/16-n

Details and patient eligibility

About

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.

Enrollment

20 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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