PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PTCy and ruxolitinib
|
Procedure: Allogeneic hematopoietic stem cell transplantation
Day 0: Infusion of unmanipulated graft
Other Names:
Drug: Busulfan
Days -5 through -3: Busulfan 1 mg/kg po qid №10
Drug: Fludarabine monophosphate
Days -7 through -2: 30 mg/m2/day iv qd x 6 days
Drug: Cyclophosphamide
Day +3 and +4: 50 mg/kg/day iv qd
Other Names:
Drug: Ruxolitinib
Days -8 through -2 15 mg tid
Drug: Ruxolitinib
Days +5 through +100: 7.5 mg bid
|
Outcome Measures
Primary Outcome Measures
- Incidence of acute graft-versus-host disease, grades II-IV [180 days]
- Incidence of chronic GVHD, moderate and severe (NIH criteria) [365 days]
Secondary Outcome Measures
- Incidence of primary or secondary graft failure [60 days]
- Non-relapse mortality analysis [365 days]
Non-relapse mortality is defined as any death in absence of relapse or progressive disease. Summarized using Kaplan-Meier and cumulative incidence estimates.
- Overall survival analysis [365 days]
Summarized using Kaplan-Meier and cumulative incidence estimates.
- Event-free survival analysis [365 days]
Event is defined as relapse or death in the specified time frame. Summarized using Kaplan-Meier and cumulative incidence estimates.
- Relapse rate analysis [365 days]
Summarized using Kaplan-Meier and cumulative incidence estimates.
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [100 days]
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
- Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence [100 days]
Eligibility Criteria
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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | First Pavlov State Medical University of St. Petersburg | Saint-Petersburg | Russian Federation | 197089 |
Sponsors and Collaborators
- St. Petersburg State Pavlov Medical University
Investigators
- Study Director: Boris V. Afanasyev, Professor, St. Petersburg State Pavlov Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 04/16-n