PTCy and Ruxolitinib GVHD Prophylaxis in Myelofibrosis

NCT02806375 | Completed Phase 1

• 1 other identifier: 04/16-n
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

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

  180 days

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

  365 days

Secondary Outcomes (7)

• Incidence of primary or secondary graft failure

  60 days

• Non-relapse mortality analysis

  365 days

• Overall survival analysis

  365 days

• Event-free survival analysis

  365 days

• Relapse rate analysis

  365 days

Study Arms (1)

PTCy and ruxolitinib

EXPERIMENTAL

Procedure: Allogeneic hematopoietic stem cell transplantation; Drug: Busulfan; Drug: Fludarabine monophosphate; Drug: Cyclophosphamide; Drug: Ruxolitinib

Interventions

Allogeneic hematopoietic stem cell transplantation PROCEDURE

Day 0: Infusion of unmanipulated graft

Also known as: HSCT

PTCy and ruxolitinib

Busulfan DRUG

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

PTCy and ruxolitinib

Fludarabine monophosphate DRUG

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

PTCy and ruxolitinib

Cyclophosphamide DRUG

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

Also known as: Cytoxan

PTCy and ruxolitinib

Ruxolitinib DRUG

Days -8 through -2 15 mg tid

PTCy and ruxolitinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, 197089, Russia

Location

Related Publications (1)

• 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.

  PMID: 32325461 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis; Myeloproliferative Disorders; Immune System Diseases

Interventions

Busulfan; fludarabine phosphate; Cyclophosphamide; ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Boris V. Afanasyev, Professor

  St. Petersburg State Pavlov Medical University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation

Study Record Dates

• First Submitted: June 8, 2016
• First Posted: June 20, 2016
• Study Start: January 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: April 1, 2019
• Last Updated: April 4, 2019

Record last verified: 2019-04

Locations

RU (1)