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…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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:
o Primary graft failure;
o Acute graft versus host disease grade 3-4;
o Secondary graft failure
o Death, whatever the cause
Secondary outcome
• Adverse events
• Proportion of patients receiving allo-SCT
• Response rate (>= PR)
• Progression free survival
• 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
Background 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
Study 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.
Study design
Phase II, single arm multicenter
Intervention
Induction with 3-4 cycles pacritinib, followed by allo-SCT if suitable donor
available. All patients will receive the same treatment.
Study burden and risks
Benefit for participating patients consists of improvement of MF-related
symptoms before allo-SCT, decrease of spleen size and thereby improvement of
clinical condition and transplantation outcome. Nevertheless, pacritinib
treatment can be associated with side-effects (gastro-intestinal).
VUMC, HOVON Centraal Bureau, De Boelelaan 1118
Amsterdam 1081 HZ
NL
VUMC, HOVON Centraal Bureau, De Boelelaan 1118
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
- Patients with a confirmed diagnosis of post-ET, post-PV or primary
myelofibrosis
- Intermediate-2 or high-risk according to DIPSS plus
- Age 18-70 years inclusive
- WHO performance status 0-2
- 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
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.
- 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-000195-98-NL |
| CCMO | NL52462.078.15 |