Exploring the potential of adding the drug Ruxolitinib to the standard reduced intensity (lower strength) chemotherapy regimen prior to bone marrow transplant in patients with myelofibrosis.

Phase 1

• Conditions: Primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) and post-essential thrombocythemia myelofibrosis (PET-MF), collectively known as myelofibrosis (MF); MedDRA version: 18.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-005010-19-GB
• Lead Sponsor: Consorzio Mario Negri Sud

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-04-16
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 86

Inclusion Criteria

1. Documented diagnosis of primary myelofibrosis according to WHO (World Health Organisation) criteria or either post PV (polycythemia vera) myelofibrosis or post ET (essential thrombocythemia) myelofibrosis as per IWG-MRT (International Working Group-Myeloproliferative Neoplasms Research and Treatment) criteria
2. Age 18–70 years
3. Intermediate- 2 / high-risk disease as per Dynamic International Prognostic Scoring System (DIPSS) criteria
OR
Intermediate- 1 risk disease with one of the following additional unfavourable features known to impact upon survival, adversely
a. Red cell transfusion dependency
b. Unfavourable Karyotype
c. Platelet count less than 100 x 109/L
4. Blasts in Peripheral Blood and Bone Marrow less than 20% prior to study enrolment
5. Availability of a suitable matched related (6/6 or 5/6) or unrelated donor (10/10 or 9/10 antigen or allele matched)
6. Able to give informed written consent
7. ECOG Performance status of 0-2
8. Life expectancy greater than 3 months
9. Off all MF-directed therapy including investigational agents for at least 2 weeks prior to study enrolment and recovered from all toxicities*
10. Adequate organ function:
• Adequate renal function – creatinine less than 1.5 x Institutional Upper Limit of Normal (IULN)
• Adequate hepatic function – Aspartate Aminotransferase / Alanine Aminotransferase (AST/ALT) less than 2.5 x IULN, Total Bilirubin less than 1.5 x IULN
• Adequate hematopoietic function – Platelet greater than or equal to 50 x 109/L and Absolute Neutrophil Count greater than or equal 1.0 x 109/L
• Left Ventricular Ejection Factor (LVEF) greater than 40% (Multiple Gated Acquisition Scan or echocardiogram) normal per institutional standard
• Adequate pulmonary function with Diffusing capacity of Lung Carbon Dioxide (DLCO) greater than 50%
* A patient who has been on stable dose of Ruxolitinib and has received treatment less than or equal to 6 months prior to the study entry will be considered potentially eligible for the study with the caveat that there is no evidence of loss of response (greater than 5cm increase in spleen size from the lowest point termed 'nadir').
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 63
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23

Exclusion Criteria

1. Any previous JAK2 inhibitor treatment prior to study enrolment, with the exception of Ruxolitinib
2. Hypersensitivity to JAK inhibitor
3. Clinical or laboratory evidence of cirrhosis
4. Prior allogeneic transplant for any hematopoietic disorder
5. Greater than 20% blast in the PB (peripheral blood)or BM (bone marrow) prior to HCT or had leukemic transformation (greater than 20% blasts in PB or BM any time prior to HCT)
6. Syngeneic donor
7. Cord Blood transplant
8. Active uncontrolled infection
9. History of another malignancy within 5-years of date of HCT except history of basal cell or squamous cell carcinoma of skin or PV or ET
10. Known Human Immunodeficiency Virus (HIV) positive
11. Pregnancy at the time of transplant
12. Any other concurrent illness which in Investigator’s opinion puts the patient at excessive risk of treatment related toxicities
13. Unable to give informed consent
14. Active infection with hepatitis A,B or C virus
15. Subjects who require therapy with a strong CYP3A4 (Cytochrome P450 3A4) inhibitor prior to enrolment to this study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified