Back to results

PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis

Primary Purpose

Primary Myelofibrosis, Myeloproliferative Disorders

Status

Completed

Phase

Phase 1

Locations

Russian Federation

Study Type

Interventional

Intervention

Allogeneic hematopoietic stem cell transplantation

Busulfan

Fludarabine monophosphate

Cyclophosphamide

Ruxolitinib

About this trial

This is an interventional treatment trial for Primary Myelofibrosis focused on measuring Myelofibrosis, Ruxolitinib, Cyclophosphamide, Immunosuppressive Agents, Immune System Diseases, Busulfan, Fludarabine, Antineoplastic Agents, Alkylating, Myeloablative Agonists, Hematopoietic Stem Cell Transplantation, Allogeneic

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

First Pavlov State Medical University of St. Petersburg

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PTCy and ruxolitinib

Arm Description

Outcomes

Primary Outcome Measures

Incidence of acute graft-versus-host disease, grades II-IV

Incidence of chronic GVHD, moderate and severe (NIH criteria)

Secondary Outcome Measures

Incidence of primary or secondary graft failure

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.

Overall survival analysis

Summarized using Kaplan-Meier and cumulative incidence estimates.

Event-free survival analysis

Event is defined as relapse or death in the specified time frame. Summarized using Kaplan-Meier and cumulative incidence estimates.

Relapse rate analysis

Summarized using Kaplan-Meier and cumulative incidence estimates.

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

Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

Full Information

NCT ID

NCT02806375

First Posted

June 8, 2016

Last Updated

April 3, 2019

Sponsor

St. Petersburg State Pavlov Medical University

1. Study Identification

Unique Protocol Identification Number

NCT02806375

Brief Title

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

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

January 2016 (Actual)

Primary Completion Date

December 2018 (Actual)

Study Completion Date

April 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

St. Petersburg State Pavlov Medical University

4. Oversight

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PTCy and ruxolitinib

Arm Type

Experimental

Intervention Type

Procedure

Intervention Name(s)

Allogeneic hematopoietic stem cell transplantation

Other Intervention Name(s)

HSCT

Intervention Description

Day 0: Infusion of unmanipulated graft

Intervention Type

Drug

Intervention Name(s)

Busulfan

Intervention Description

Days -5 through -3: Busulfan 1 mg/kg po qid №10

Intervention Type

Drug

Intervention Name(s)

Fludarabine monophosphate

Intervention Description

Days -7 through -2: 30 mg/m2/day iv qd x 6 days

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan

Intervention Description

Day +3 and +4: 50 mg/kg/day iv qd

Intervention Type

Drug

Intervention Name(s)

Ruxolitinib

Intervention Description

Days -8 through -2 15 mg tid

Intervention Type

Drug

Intervention Name(s)

Ruxolitinib

Intervention Description

Days +5 through +100: 7.5 mg bid

Primary Outcome Measure Information:

Title

Incidence of acute graft-versus-host disease, grades II-IV

Time Frame

180 days

Title

Incidence of chronic GVHD, moderate and severe (NIH criteria)

Time Frame

365 days

Secondary Outcome Measure Information:

Title

Incidence of primary or secondary graft failure

Time Frame

60 days

Title

Non-relapse mortality analysis

Description

Non-relapse mortality is defined as any death in absence of relapse or progressive disease. Summarized using Kaplan-Meier and cumulative incidence estimates.

Time Frame

365 days

Title

Overall survival analysis

Description

Summarized using Kaplan-Meier and cumulative incidence estimates.

Time Frame

365 days

Title

Event-free survival analysis

Description

Event is defined as relapse or death in the specified time frame. Summarized using Kaplan-Meier and cumulative incidence estimates.

Time Frame

365 days

Title

Relapse rate analysis

Description

Summarized using Kaplan-Meier and cumulative incidence estimates.

Time Frame

365 days

Title

Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

Description

Time Frame

100 days

Title

Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

Time Frame

100 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boris V. Afanasyev, Professor

Organizational Affiliation

St. Petersburg State Pavlov Medical University

Official's Role

Study Director

Facility Information:

Facility Name

First Pavlov State Medical University of St. Petersburg

City

Saint-Petersburg

ZIP/Postal Code

197089

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

Consultations with lawyers are ongoing about how IPD initiative fits the local law "About personal data 152-fz".

Citations:

PubMed Identifier

32325461

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.

Results Reference

derived

Learn more about this trial

PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis

We'll reach out to this number within 24 hrs