AzTrials
AzTrials

MyelofibrosisPhase 2HOVON134MFNCT03645824

Myelofibrosis Treated With Pacritinib Before aSCT. (HOVON134MF)

A Phase 2 study testing Pacritinib in people with Myelofibrosis, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 12 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The only curative treatment for patients with myelofibrosis (MF) is allogeneic stem cell transplantation (SCT). Treatment with JAK2 inhibitors like pacritinib improves condition of MF patients, decreases spleen size and might diminish graft-versus-host disease (GvHD), thereby improving the outcome of SCT. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Myelofibrosis
What is being tested?
Pacritinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
12 sitesin 2 countries
Study dates
4 Jun 2018to Feb 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with a confirmed diagnosis of post-ET, post-PV or primary myelofibrosis
  • 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

Who cannot join

  • 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
Show all 21Show fewer
  • 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

Trial locations and contacts

12 sites in 2 countries.

12 sites in 2 countries

Netherlands8 sites

  • NL-Amsterdam-AMC

    Amsterdam

  • NL-Amsterdam-VUMC

    Amsterdam

  • NL-Groningen-UMCG

    Groningen

  • NL-Maastricht-MUMC

    Maastricht

  • NL-Nijmegen-RADBOUDUMC

    Nijmegen

  • NL-Rotterdam-EMCDANIEL

    Rotterdam

  • NL-Rotterdam-ERASMUSMC

    Rotterdam

  • NL-Utrecht-UMCUTRECHT

    Utrecht

Other trials in Netherlands

Belgium4 sites

  • BE-Antwerpen-ZNASTUIVENBERG

    Antwerp

  • BE-Gent-UZGENT

    Ghent

  • BE-Leuven-UZLEUVEN

    Leuven

  • BE-Roeselare-AZDELTA

    Roeselare

Other trials in Belgium

About this study

Official title: A Phase II Trial in Patients With Myelofibrosis (Primary, Post-ET or Post PV-MF) Treated With the Selective JAK2 Inhibitor Pacritinib Before Reduced-intensity Conditioning Allogeneic Stem Cell Transplantation

The only curative treatment for patients with myelofibrosis (MF) is allogeneic stem cell transplantation (SCT). Treatment with JAK2 inhibitors like pacritinib improves condition of MF patients, decreases spleen size and might diminish graft-versus-host disease (GvHD), thereby improving the outcome of SCT.

Read the detailed description

Despite recent new therapeutic options, allogeneic Stem Cell Transplantation remains the only curative option in patients with Myelofibrosis. Therefore, optimalization of this therapy remains a major challenge. Improvement of the clinical condition of these patients, decreasing spleen size can be accomplished by JAK2 inhibitor treatment and might improve SCT outcome. In addition, selective JAK2 inhibitors might modulate GvHD which can also add to improved SCT outcome. Also, decreasing the burden/activity of the disease before allo-SCT might also improve final disease response. The first, limited, clinical data of ruxolitinib treatment before allo-SCT show controversial effects on the outcome of SCT. Therefore, additional prospective clinical trials have to be done to establish the role of JAK2 inhibition before allogeneic SCT. Since ruxolitinib has considerable myelosuppressive effects which might limit the clinical use in some MF patients, other selective JAK2 inhibitors might be useful in this setting. Pacritinib, as a JAK2/FLT3 inhibitor, has a very potent JAK2 inhibitory activity without myelosuppressive effects and might therefore be more suitable than ruxolitinib. The major possible side effects are gastro-intestinal and can be managed with medication. In several studies, pacritinib has shown to be effective in decreasing spleen size and has shown to improve clinical condition of patients. Therefore, this compound seems promising in improving the outcome of allo-SCT. Although pacritinib causes no inhibition of JAK1 activity and therefore might have limited effects in decreasing inflammatory response, this might also be of benefit since a "withdrawal syndrome" as has been described after cessation of ruxolitinib is not to be expected.

With this trial, using pacritinib treatment before allo-SCT, the issue of improvement of SCT outcome will be investigated.

Conditions
Myelofibrosis
Being tested
Pacritinib
Keywords
Hemato-Oncology, Allogeneic Stem Cell Transplantation, Pacritinib, JAK2 inhibitor, Myelofibrosis
Medical subject headings
Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PacritinibDrug

    Patients receive up to 4 cycles of pacritinib before allo-SCT

Study groups in NCT03645824
Study groupRoleWhat they receive
Pacritinib treatment befor allo-SCTExperimentalThe effect of pacritinib treatment during 3 to 4 cycles before allo-SCT on engraftment 6 months (day +180) post allo-SCT in MF patients.
Receives: Drug: Pacritinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients receiving allo-SCT, with failure within or at day 180 post-transplant.

    Failure can be defined by one of the following parameters:

    • Primary graft failure
    • Acute graft versus host disease grade 3-4
    • Secondary graft failure
    • Death, from any cause

    Measured: 2 years

Secondary outcomes (6)

  1. Adverse events

    Adverse events will be monitored.

    Measured: 5 years

  2. Progression free survival

    Progression free survival as time between registration or SCT until progression/relapse or death from any cause

    Measured: 5 years

  3. Overall survival

    Over all survival, calculated from either registration or SCT.

    Measured: 5 years

  4. Relapse mortality

    Death due to the disease or after progression

    Measured: 5 years

  5. Non-relapse mortality

    Death not due to disease or relapse

    Measured: 5 years

  6. Quality of life during and after treatment

    Quality of life during and after treatment will be recorded by use of the MPN-SAF questionnaire.

    From a total of 27 questions, the scores (from 0 to 10) from the following 10 questions are added and subsequently averaged to come to a total quality of life score.

    • fatigue
    • satisfction after a meal
    • stomach complaints
    • not able to perform activities
    • concentration problems
    • night sweat
    • itch
    • bone pain
    • fever
    • sudden weight loss

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Aug 2018
  2. Study start4 Jun 2018
  3. Primary completionJul 2023 (estimated)
  4. Study completionFeb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03645824
Sponsor's protocol ID
HO134
Other IDs
2015-000195-98, 2015
Acronym
HOVON134MF
Status last verified
Aug 2022
First submitted
26 Mar 2018
Last updated
22 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pacritinib in people with Myelofibrosis, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 12 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Netherlands, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients receiving allo-SCT, with failure within or at day 180 post-transplant. (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03645824.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in