Clinical Trials Register

Summary
EudraCT Number:	2015-000195-98
Sponsor's Protocol Code Number:	HO134
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-02-03
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2015-000195-98

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

HOVON 134 MF

A.4.1

Sponsor's protocol code number

HO134

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	HOVON Foundation
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Dutch Cancer Society
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	CTI
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	HOVON
B.5.2	Functional name of contact point	HOVON Data Center
B.5.3	Address:
B.5.3.1	Street Address	P.O. Box 2040
B.5.3.2	Town/ city	Rotterdam
B.5.3.3	Post code	3000 CA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+310107041560
B.5.5	Fax number	+310107041028
B.5.6	E-mail	secretariaatctc@erasmusmc.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/10/768
D.3 Description of the IMP
D.3.1	Product name	Pacritinib
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	pacritinib
D.3.9.1	CAS number	937272-79-2
D.3.9.3	Other descriptive name	PACRITINIB
D.3.9.4	EV Substance Code	SUB114513
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Primary myelofibrosis
Polycythemia vera
Essential thrombocytosis

E.1.1.1

Medical condition in easily understood language

Primary myelofibrosis
Polycythemia vera
Essential thrombocytosis

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10074689
E.1.2	Term	Post polycythemia vera myelofibrosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10074690
E.1.2	Term	Post essential thrombocythemia myelofibrosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10028537
E.1.2	Term	Myelofibrosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

-Assess effect of pacritinib treatment on splenomegaly
-Improve disease response by pacritinib treatment and allo-SCT
-Determine proportion of patients receiving allo-SCT
-Document safety and toxicity of pacritinib treatment before allo-SCT
-Compare effect of treatment on marrow fibrosis by DCE-MRI scan
-Evaluate efficacy of induction therapy determined as time to response
-Determine time to red cell recovery after SCT
-Determine progression free survival and overall survival from study inclusion and separately from allo-SCT in transplanted patients
-Evaluate NRM (Non-Relapse -Mortality) from inclusion and separately after allo-SCT in transplanted patients
-Determine effects on JAK2, calreticulin or mpl (allelic) burden before and after allo-SCT and donor (micro) chimerism
-Summarize Quality-of-Life (QOL) during/after treatment using the MPN-SAF scoring tool
-Determine effects on inflammatory cytokines
-Determine prognostic value of additional molecular markers

E.2.3

Trial contains a sub-study

E.3

Principal 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 F)
-Age 18-70 years inclusive
-WHO performance status 0-2 (Appendix C)
Platelet count ≥ 25 × 109/L without platelet support within 2 weeks before study entry.
-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

E.4

Principal exclusion criteria

- Patients who have been treated with pacritinib as their previous JAK2 inhibitor treatment cannot participate in this study.
- Previous treatment with JAK2 inhbitors, other than pacritinib, is allowed with the exception of high dose ruxolitinib (above 10 mg BID). For these patients taper the dose to 10 mg BID or lower at least 2 weeks before pacritinib treatment is allowed.
- 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.
-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

E.5 End points

E.5.1

Primary end point(s)

Among the patients who received an allo-SCT, the proportion of patients with failure within or at D180 post-transplant. Events that are considered a failure are:
-Primary graft failure;
-Acute graft versus host disease grade 3-4;
-Secondary graft failure;
-Death, whatever the cause

E.5.1.1

Timepoint(s) of evaluation of this end point

When data of the patients is available.

E.5.2

Secondary end point(s)

• Adverse events
• Proportion of patients receiving allo-SCT
• Response rate (≥ PR) (see appendix B)
• Progression free survival (PFS, i.e. time from either registration or allo-SCT until progression/relapse or death from any cause, whichever comes first)
• Overall survival (OS) calculated from either registration or allo-SCT. Patients still alive or lost to follow up are censored at the date they were last known to be alive
• Relapse mortality (RM), i.e. death due to the disease or after progression
• Non-relapse mortality(NRM)
• Quality of Life during/after treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

When the data of patients is available.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	HOVON Foundation
G.4.3.4	Network Country	Netherlands

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-02-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-08-18

P. End of Trial
P.	End of Trial Status	Ongoing

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