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Clinical picture: Benign

Trial: HOVON 134 MF


News
1. Overview
Study details
2. Patient eligibility criteria
3. Registration (& randomization) of patients
4. Participating parties
5. Participating sites
6. Instruction videos
7. Download documentation / forms


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1. Overview



Summary

A Phase II, single arm multicenter trial, using pacritinib pretreatment in patients with myelofibrosis (primary, post-ET or post PV-MF) before allo-SCT.
The improvement of SCT outcome will be investigated. SCT outcome will be studied at 180 days post SCT, defining SCT failure as the occurrence of primary graft failure, secondary graft failure, the occurrence of grade 3-4 GvHD or death.


Status

open


Members

HOVON



Study details



Echelon level

Level A


Echelon level specification

Allo transplantation centers


Type of monitoring for this study

Site evaluation visits


Target number of patients

70


Current number of patients

14


Date of first EC&CA submission

18-Nov-2015


Date of activation

15-Sep-2017


Approved by

METC Erasmus MC Rotterdam
CCMO


Study objectives

Primary Objective:
Improve allo-SCT transplant outcome using a uniform conditioning regimen and pacritinib pretreatment by means of the proportion of patients with a failure within 6 months post-transplant. Events that are considered a failure are: primary graft failure; secondary graft failure; acute GvHD grade 3-4; death whatever the cause is

Secondary objectives
• To assess the effect of pacritinib treatment on splenomegaly
• To improve disease response by pacritinib treatment and allo-SCT as defined by the IWG-MRT response criteria
• To determine the proportion of patients receiving allo-SCT
• To document safety and toxicity of pacritinib treatment before allo-SCT
• To compare the effect of the treatment on marrow fibrosis by DCE-MRI scan at study entry, before SCT and 6 months post-SCT and bone marrow biopsy
• To evaluate efficacy of induction therapy determined as time to response
• To determine time to red cell recovery (red blood cell transfusion incidence for >4 weeks) after SCT
• To determine progression free survival and overall survival from study inclusion and separately from allo-SCT in transplanted patients
• To evaluate NRM (Non-Relapse -Mortality) from inclusion and separately after allo-SCT in transplanted patients
• To determine effects on JAK2, calreticulin or mpl (allelic) burden before and after allo-SCT (allelic burden before pacritinib treatment, at conditioning and monthly 1-4, 6 and 12 months post SCT) and donor (micro) chimerism
• To summarize Quality-of-Life (QOL) during/after treatment using the MPN-SAF scoring tool
• To determine effects on inflammatory cytokines at study entry, before start conditioning and 3 and 6 months after allo-SCT
• To determine the prognostic value of additional molecular markers ( ASXL1, TET2, SRSF2, DNMT3A, EZH2, CBL, IDH1,2, Lnk, SF3B1)


2. Patient eligibility criteria



Inclusion criteria

• Patients with a confirmed diagnosis of post-ET, post-PV or primary myelofibrosis (Appendix A)
• Intermediate-2 or high-risk according to DIPSS plus (Appendix E)
• Age 18-70 years inclusive
• WHO performance status 0-2 (Appendix C)
• All men and women of childbearing potential must agree to use adequate contraception during the study
• Written informed consent
• Patient is capable of giving informed consent


Exclusion criteria

• Previous treatment with JAK2 inhibitors within 2 weeks of study inclusion. Patients who have been treated with pacritinib as their previous JAK2 inhibitor treatment cannot participate in this study
• Any GI or metabolic condition (e.g. inflammatory or chronic functional bowel disorder such as Crohn’s Disease, Inflammatory Bowel Disease, chronic diarrhea or constipation) that could interfere with absorption of oral medication
• Left ventricular cardiac ejection fraction of ≤ 45% by echocardiogram or multigated acquisition (MUGA) scan
• Impaired liver and renal function, defined by liver transaminases (aspartate aminotransferase [AST]/serum glutamic oxaloacetic transaminase [SGOT] and alanine aminotransferase [ALT]/serum glutamic pyruvic transaminase [SGPT]), >3 × the upper limit of normal (ULN) (AST/ALT >5 × ULN if transaminase elevation is related to MF), direct bilirubin >4× ULN, and creatinine clearance ˂ 40 ml/min.
• Impaired coagulation function, defined by prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (APTT)>1.5 x ULN.
• Experimental treatment within four weeks before inclusion for PMF, Post-PV, or Post-ET MF
• Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D)
• Treatment with a potent strong CYP3A4 inhibitor or a strong cytochrome P450 (CYP450) inducer within the last 2 weeks
• Treatment with anticoagulation or antiplatelet agents, except for aspirin dosages of ≤100 mg per day, within the last 2 weeks
• New York Heart Association Class II, III, or IV congestive heart failure
• QTc prolongation >450 ms as assessed by ECG and corrected by Federicia method or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], family history of long QT interval syndrome, or concomitant use of medications that may prolong QT interval)
• Significant recent bleeding history defined as NCI CTCAE grade ≥2 within the last 3 months, unless precipitated by an inciting event (e.g., surgery, trauma, injury)
• Any history of CTCAE grade ≥2 non-dysrhythmia cardiac conditions within the last 6 months. Patients with asymptomatic grade 2 non-dysrhythmia cardiac conditions may be considered for inclusion, with the approval of the principal investigator, if stable and unlikely to affect patient safety.
• Any history of CTCAE grade 2 cardiac dysrhythmias within the last 6 months. Patients with non-QTc CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, with the approval of the principal investigator, if the dysrhythmias are stable, asymptomatic, and unlikely to affect patient safety.
• Patients with active, uncontrolled infections
• Patients known to be HIV (human immunodeficiency virus)-positive
• Active hepatitis A, B or C
• History of active malignancy during the past 3 years, except basal carcinoma of the skin or stage 0 cervical carcinoma
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)
• Pregnant or breastfeeding women
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule


3. Registration (& randomization) of patients



Registration

Eligible patients should be registered before start of treatment. Patients need to be registered at the HOVON Data Center by one of the following options:
• Trial Online Process (TOP, https://www.hdc.hovon.nl/top). A logon to TOP can be requested at the HOVON Data Center for participants.
• By faxing the completed registration/randomization CRF +31.10.7041028 Monday through Friday, from 09:00 to 17:00 CET
• By phone +31.10.7041560 Monday through Friday, from 09:00 to 17:00 CET


Registration criteria

The following information will be requested:



The following information will be requested at registration:
• Protocol number
• Institution name
• Name of caller/responsible investigator
• Sex
• Age on inclusion and year of birth
• Date written informed consent
• Specific items patient gives consent for (see ICF)
• Eligibility criteria


4. Participating parties



Principal Investigator(s)

Dhr. Dr. P.A.W. te Boekhorst (Erasmus MC - Centrum)


Statistician(s)

Dhr. Dr. B. van der Holt (Erasmus MC - Daniel)


Monitor - Site Evaluation Visits

MonitorTeamHDC (Erasmus MC - Daniel)


Other functions

Central Coordinator - Special Investigations - Dhr. Dr. E. Braakman (Erasmus MC - Medische Faculteit)
Central Coordinator - Special Investigations - Dhr. Dr. B.A. van der Reijden (Radboudumc)
Reviewer - Cytogenetics - Mw. Dr. H.B. Beverloo (Erasmus MC - Medische Faculteit)
Reviewer - Pathology - Dr. K.M. Hebeda (Radboudumc)
Reviewer - Pathology - Dhr. Dr. K.H. Lam (Erasmus MC - Centrum)


Principal investigator

dr. P. te Boekhorst


Trial manager

M. Kap (m.kap.1@erasmusmc.nl)


Central data management

Christel van Hooije (c.vanhooije@erasmusmc.nl)


5. Participating sites



Site
Included patients *
BE-Antwerpen-ZNA Stuivenberg
1
BE-Gent-UZ Gent
0
BE-Leuven-UZ Gasthuisberg
0
BE-Roeselare-AZDelta
1
NL-Amsterdam-AMC
2
NL-Amsterdam-VUMC
3
NL-Maastricht-AZ Maastricht
1
NL-Nijmegen-Radboudumc
1
NL-Rotterdam-Erasmus MC - Centrum
5

* Please note that if TOP is not used to register patients for a study, the number of patients shown is zero.

6. Instruction videos



7. Download documentation / forms


 Protocol

 Patient Information & IC form (NL)



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