PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis

Primary Myelofibrosis Clinical Trial

Official title:

Graft-versus-host Disease Prophylaxis With Post-transplantation Cyclophosphamide and Ruxolitinib in Patients With Myelofibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02806375
• Other study ID #: 04/16-n
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2016
• Est. completion date: April 2019

Study information

• Verified date: April 2019
• Source: St. Petersburg State Pavlov Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Myeloproliferative Disorders
• Primary Myelofibrosis

Intervention

Procedure:
• Allogeneic hematopoietic stem cell transplantation
Day 0: Infusion of unmanipulated graft

Drug:
• Busulfan
Days -5 through -3: Busulfan 1 mg/kg po qid ?10
• Fludarabine monophosphate
Days -7 through -2: 30 mg/m2/day iv qd x 6 days
• Cyclophosphamide
Day +3 and +4: 50 mg/kg/day iv qd
• Ruxolitinib
Days -8 through -2 15 mg tid
• Ruxolitinib
Days +5 through +100: 7.5 mg bid

Locations

Country	Name	City	State
Russian Federation	First Pavlov State Medical University of St. Petersburg	Saint-Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
St. Petersburg State Pavlov Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of acute graft-versus-host disease, grades II-IV		180 days
Primary	Incidence of chronic GVHD, moderate and severe (NIH criteria)		365 days
Secondary	Incidence of primary or secondary graft failure		60 days
Secondary	Non-relapse mortality analysis	Non-relapse mortality is defined as any death in absence of relapse or progressive disease. Summarized using Kaplan-Meier and cumulative incidence estimates.	365 days
Secondary	Overall survival analysis	Summarized using Kaplan-Meier and cumulative incidence estimates.	365 days
Secondary	Event-free survival analysis	Event is defined as relapse or death in the specified time frame. Summarized using Kaplan-Meier and cumulative incidence estimates.	365 days
Secondary	Relapse rate analysis	Summarized using Kaplan-Meier and cumulative incidence estimates.	365 days
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	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	100 days
Secondary	Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence		100 days