JAK2 Inhibitors RUXOLITINIB in Patients With Myelofibrosis

Phase 2

Completed

• Conditions: Myelofibrosis
• Interventions: Drug: Ruxolotinib

• Registration Number: NCT01795677
• Lead Sponsor: French Innovative Leukemia Organisation

Brief Summary

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

Detailed Description

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

Study Timeline

• Study Start: 2012-12
• Study First Submitted: 2012-12-21
• Study First Submitted QC: 2013-02-18
• Study First Posted: 2013-02-21
• Primary Completion: 2018-05
• Study Completion: 2019-03
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-26
• Last Update Posted: 2022-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 78

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RUXOLOTINIB	Ruxolotinib	Ruxolotinib : patient with donor HSCT 4 months later patients without donor: ruxolotinib alone

Primary Outcome Measures

Name	Time	Method
DFS	24 months after inclusion	DFS is defined as the probability to be alive and in remission

Secondary Outcome Measures

Name	Time	Method
PATIENTS CARACTERISTICS	24 months after inclusion	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
HSCT	24 months after inclusion	* 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)

Trial Locations

Locations (1)

ROBIN; 🇫🇷 Paris, France