Clinical trial NCT02806375: PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis
Official title: Graft-versus-host Disease Prophylaxis With Post-transplantation Cyclophosphamide and Ruxolitinib in Patients With Myelofibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Primary Myelofibrosis
Myeloproliferative Disorders
Keywords: Myelofibrosis
Ruxolitinib
Cyclophosphamide
Immunosuppressive Agents
Immune System Diseases
Busulfan
Fludarabine
Antineoplastic Agents, Alkylating
Myeloablative Agonists
Hematopoietic Stem Cell Transplantation
Allogeneic
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2016-06-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Incidence of acute graft-versus-host disease, grades II-IV
timeFrame: 180 days
measure: Incidence of chronic GVHD, moderate and severe (NIH criteria)
timeFrame: 365 days
Secondary outcomes:
measure: Incidence of primary or secondary graft failure
timeFrame: 60 days
measure: Non-relapse mortality analysis
timeFrame: 365 days
measure: Overall survival analysis
timeFrame: 365 days
measure: Event-free survival analysis
timeFrame: 365 days
measure: Relapse rate analysis
timeFrame: 365 days
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: 100 days
measure: Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence
timeFrame: 100 days
Other outcomes:
Locations:
city: Saint-Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St. Petersburg
Study officials:
affiliation: St. Petersburg State Pavlov Medical University
name: Boris V. Afanasyev, Professor
role: STUDY_DIRECTOR
References:
citation: Morozova EV, Barabanshikova MV, Moiseev IS, Shakirova AI, Barhatov IM, Ushal IE, Rodionov GG, Moiseev SI, Surkova EA, Lapin SV, Vlasova JJ, Rudakova TA, Darskaya EI, Baykov VV, Alyanski AL, Bondarenko SN, Afanasyev BV. A Prospective Pilot Study of Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide and Ruxolitinib in Patients with Myelofibrosis. Acta Haematol. 2021;144(2):158-165. doi: 10.1159/000506758. Epub 2020 Apr 23.