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PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02806375
Recruitment Status : Completed
First Posted : June 20, 2016
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
Ivan S Moiseev, St. Petersburg State Pavlov Medical University

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
Primary Myelofibrosis Myeloproliferative Disorders Procedure: Allogeneic hematopoietic stem cell transplantation Drug: Busulfan Drug: Fludarabine monophosphate Drug: Cyclophosphamide Drug: Ruxolitinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Graft-versus-host Disease Prophylaxis With Post-transplantation Cyclophosphamide and Ruxolitinib in Patients With Myelofibrosis
Actual Study Start Date : January 2016
Actual Primary Completion Date : December 2018
Actual Study Completion Date : April 2019


Arm Intervention/treatment
Experimental: PTCy and ruxolitinib Procedure: Allogeneic hematopoietic stem cell transplantation
Day 0: Infusion of unmanipulated graft
Other Name: HSCT

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 Name: Cytoxan

Drug: Ruxolitinib
Days -8 through -2 15 mg tid

Drug: Ruxolitinib
Days +5 through +100: 7.5 mg bid




Primary Outcome Measures :
  1. Incidence of acute graft-versus-host disease, grades II-IV [ Time Frame: 180 days ]
  2. Incidence of chronic GVHD, moderate and severe (NIH criteria) [ Time Frame: 365 days ]

Secondary Outcome Measures :
  1. Incidence of primary or secondary graft failure [ Time Frame: 60 days ]
  2. Non-relapse mortality analysis [ Time Frame: 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.

  3. Overall survival analysis [ Time Frame: 365 days ]
    Summarized using Kaplan-Meier and cumulative incidence estimates.

  4. Event-free survival analysis [ Time Frame: 365 days ]
    Event is defined as relapse or death in the specified time frame. Summarized using Kaplan-Meier and cumulative incidence estimates.

  5. Relapse rate analysis [ Time Frame: 365 days ]
    Summarized using Kaplan-Meier and cumulative incidence estimates.

  6. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 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

  7. Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence [ Time Frame: 100 days ]


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02806375


Locations
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Russian Federation
First Pavlov State Medical University of St. Petersburg
Saint-Petersburg, Russian Federation, 197089
Sponsors and Collaborators
St. Petersburg State Pavlov Medical University
Investigators
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Study Director: Boris V. Afanasyev, Professor St. Petersburg State Pavlov Medical University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ivan S Moiseev, Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, St. Petersburg State Pavlov Medical University
ClinicalTrials.gov Identifier: NCT02806375    
Other Study ID Numbers: 04/16-n
First Posted: June 20, 2016    Key Record Dates
Last Update Posted: April 4, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Consultations with lawyers are ongoing about how IPD initiative fits the local law "About personal data 152-fz".
Keywords provided by Ivan S Moiseev, St. Petersburg State Pavlov Medical University:
Myelofibrosis
Ruxolitinib
Cyclophosphamide
Immunosuppressive Agents
Immune System Diseases
Busulfan
Fludarabine
Antineoplastic Agents, Alkylating
Myeloablative Agonists
Hematopoietic Stem Cell Transplantation
Allogeneic
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Cyclophosphamide
Busulfan
Fludarabine
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites