Graft-versus-host Disease Prophylaxis With Post-transplantation Cyclophosphamide and Ruxolitinib in Patients With Myelofibrosis
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- St. Petersburg State Pavlov Medical University
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Incidence of chronic GVHD, moderate and severe (NIH criteria)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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-DQB
- •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
Arms & Interventions
PTCy and ruxolitinib
Intervention: Allogeneic hematopoietic stem cell transplantation (Procedure)
PTCy and ruxolitinib
Intervention: Busulfan (Drug)
PTCy and ruxolitinib
Intervention: Fludarabine monophosphate (Drug)
PTCy and ruxolitinib
Intervention: Cyclophosphamide (Drug)
PTCy and ruxolitinib
Intervention: Ruxolitinib (Drug)
Outcomes
Primary Outcomes
Incidence of chronic GVHD, moderate and severe (NIH criteria)
Time Frame: 365 days
Incidence of acute graft-versus-host disease, grades II-IV
Time Frame: 180 days
Secondary Outcomes
- Incidence of primary or secondary graft failure(60 days)
- Event-free survival analysis(365 days)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.03(100 days)
- Non-relapse mortality analysis(365 days)
- Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence(100 days)
- Overall survival analysis(365 days)
- Relapse rate analysis(365 days)
Investigators
Ivan S Moiseev
Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation
St. Petersburg State Pavlov Medical University