JAK2 Inhibitors RUXOLITINIB in Patients With Myelofibrosis

JAK2 Inhibitors RUXOLITINIB in Patients With High or Intermediate Risk Primary or Secondary Myelofibrosis Eligible for Allogeneic Stem Cell Transplantation: a Prospective Multicentric Phase II Study

JAK2 inhibitor RUXOLITINIB before allogeneic hematopoietic stem cell transplantation (HSCT) in patients with primary or secondary myelofibrosis : a prospective phase II

Study Overview

• Status: Completed
• Conditions: Myelofibrosis
• Intervention / Treatment: Drug: Ruxolotinib

Detailed Description

JAK2 inhibitor RUXOLITINIB before allogeneic hematopoietic stem cell transplantation (HSCT) in patients with primary or secondary myelofibrosis

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • ROBIN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 67 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18 and 69 years

• No comorbidity contraindicating the transplantation :

  • Severe respiratory failure defined as dyspnea grade III or more
  • Severe cardiac failure defined as EF < or = 30%
  • Severe renal failure defined as creatinine clearance < 30 ml/min or dialysis
  • Dementia or non-ability to give informed consent for the protocol
  • Major alteration of performance status defined as ECOG > 2
  • Severe liver disease defined as a cirrhosis or bilirubin > 2 x ULN, or AST/ALT > 5 x ULN
• Primary or secondary myelofibrosis diagnosed according to WHO definition (Tefferi, et al 2007)
• Palpable splenomegaly or splenomegaly measured by any imagery (maximum size> 15 cm by ultrasound scan, Magnetic Resonance Imaging or computer tomography)
• Disease if intermediate or high risk according to published criteria and summarized as follows:

At least one criterion among the following:

• Haemoglobin < 100 gr/L (unrelated to medication toxicity)
• Leucocytes < 4 G/L (unrelated to medication toxicity) or > 25 G/L
• Poor prognosis cytogenetics : complex karyotype, abnormalities of chromosomes 5, 7 or 17 , +8, 12p-, inv(3), 11q23

Two criteria among the following criteria :

• General symptoms (weight lost > 10% in less than 6 months, night swears, specific fever > 37.5°C)
• Peripheral blastosis > 1% observed at least twice
• Thrombocytopenia < 100 G/L (unrelated to treatment toxicity)

Exclusion Criteria:

• Myelofibrosis transformed into acute leukaemia with 20% blasts of more in blood or bone marrow
• Previous treatment with JAK2 inhibitor
• Thrombopenia < 50 G/L
• Comorbidities contraindicating the transplantation
• Comorbidity score Sorror > 3
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RUXOLOTINIB; Ruxolotinib : patient with donor HSCT 4 months later patients without donor: ruxolotinib alone	Drug: Ruxolotinib; Ruxolotinib doses calculated with platelets count and P450 cytochrome inhibitor HSCT for patients with donor; Other Names: Kakavi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS	DFS is defined as the probability to be alive and in remission	24 months after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HSCT	Rate of pre-graft splenectomy; Co-morbidity score defined by Sorror et al before RUXOLITINIB and after 4-month treatment just before transplantation; Post-graft haematological recovery: time to neutrophil engraftment, platelet and red blood cells transfusion independency; Acute GVHD grade II-IV incidence; Chronic GVHD incidence; Overall survival, disease-free survival, non-relapse mortality; JAK2V617E allele burden and status at registration, 3, 7, 16 months after inclusion (centralization)	24 months after inclusion
PATIENTS CARACTERISTICS	Patients with and without donor; Rate of patients with donor who benefit from a transplantation:; Comorbidity score at registration and after 3 months; Platelet and red blood cells transfusion independency; Performance status evolution (ECOG); General symptoms related to myelofibrosis (questionnaire MF SAF); Comparison of haematological response in patients with or without donor; Spleen size evolution; Comparison of quality of life in patients with and without (questionnaire EORTC); Comparison of overall survival in patients with and without donor; Incidence of severe infections; Cytokine measure at registration, 3, and 7 months after inclusion (centralization); MPL JAK status (at registration, centralization	24 months after inclusion

Collaborators and Investigators

• Sponsor: French Innovative Leukemia Organisation
• Investigators: Principal Investigator: MARIE ROBIN, MD, FIM/GOELAMS

Publications and helpful links

Helpful Links

• FILO internet site

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: December 21, 2012
• First Submitted That Met QC Criteria: February 18, 2013
• First Posted (Estimate): February 21, 2013

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: JAK2 inhibitor RUXOLITINIB; Primary or secondary myelofibrosis
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: JAK ALLO STUDY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No