PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis

• Status: Completed
• Trial end date: 2019-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Petersburg State Pavlov Medical University
• Treatments: Antineoplastic Agents, Alkylating; Busulfan; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Vidarabine

Criteria

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