Primary Objective:To compare the efficacy of pacritinib with that of Best Available Therapy (BAT) in patients with PMF, PPV-MF, or PET-MF; the efficacy measure for this analysis is the proportion of patients achieving a * 35% reduction in spleen…
ID
Source
Brief title
Condition
- Haematological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Study objective:
Primary efficacy objective:
- The proportion of patients achieving a * 35% reduction in spleen volume from
baseline to Week 24 by MRI or CT.
Secondary outcome
The key secundary objective is the proportion of patients with 50% reduction
in total score from baseline to Week 24 on the Myeloproliferative Neoplasm
Symptom Assessment Form (MPN-SAF TSS2.0).
Other secundary objectives are:
- Proportion of patients with a baseline platelet count < 100,000/µL achieving
> 35% reduction in spleen volume from baseline to Week 24 as measured by MRI or
CT
- Proportion of patients with a baseline platelet count < 100,000/µL achieving
> 50% reduction in the TSS from baseline to Week 24
- Proportion of patients with a baseline platelet count < 50,000/µL achieving >
35% reduction in spleen volume from baseline to Week 24 as measured by MRI or CT
- Proportion of patients with a baseline platelet count < 50,000/µL achieving >
50% reduction in in the TSS from baseline to Week 24
Background summary
For a subgroup of patients with myelofibrosis (MF) with low platelet counts,
the almost approved JAK inhibitor requires significant dose reduction and is
less effective than in patients with normal platelet counts.
Data from two phase 2 trials show that pacritinib can be safely administered to
patients with MF, including those who also have thrombocytopenia. Pacritinib
led to clinically meaningful reduction in spleen size and volume in a
substantial proportion of patients with MF. Pacritinib improved disease-related
symptoms. These effects were observed in patients with thrombocytopenia,
including those with platelet counts < 100,000/ul, as well in those with normal
platelet counts. These findings warrant phase 3 investigation to confirm the
efficacy and safety of pacritinib, both in patients with normal and those with
low platelet counts.
Study objective
Primary Objective:
To compare the efficacy of pacritinib with that of Best Available Therapy (BAT)
in patients with PMF, PPV-MF, or PET-MF; the efficacy measure for this analysis
is the proportion of patients achieving a * 35% reduction in spleen volume from
baseline to Week 24 by MRI or CT
Secundary Objective:
The key secundary objective is to compare pacritinib with BAT with respect to
the proportion of patients with * 50% reduction in total score from baseline to
Week 24 on the MPN-SAF TSS2.0.
Study design
This is an open randomized trial.
Intervention
The Pacritinib group:
The start dose is 4 x 100 mg capsules Pacritinib, once per day orally, at the
same time of day, with or without food.
A maximum of two dose reductions is allowed. The first dose reduction will be a
100-mg reduction from the original dose (reduction from 400 mg/day to 300
mg/day). The second dose reduction will be another 100-mg reduction (reduction
from 300 mg/day to 200 mg/day). Once the dose is reduced, no re-escalation is
allowed.
Best Available Therapy group:
Patients in the best available therapy group will NOT receive Pacritinib, but
the research physician will chose the best available treatment. The treatment
can be changed at any moment during the study and it is not allowed to use
investigational drugs. At Week 24 or based on the test results patients my be
eligible to cross over to the Pacritinib group during the study.
Study burden and risks
Pacritinib has been investigated in 130 patients with myelofibrosis, including
PMF and Post PV/ET MF. The most common adverse events (in at least 10% of the
patients) that do or do not have a relationship with the study medication are
low platelet counts (thrombocytopenia), low red blood cell count (anemia),
diarrhea, nausea, vomiting and fatigue. Many of these adverse events are also
symptoms of the disease.
Possible adverse events of blood collection and bone marrow tests are pain,
fatigue, bruising, painful and sensitivity of the collection spot and in rare
cases an infection could occur.
Possible adverse events of the tape that is put on the skin when making an ECG
are rash or mild irritation of the skin.
During a CT-scan of the abdomen patients are exposed to radiation. The dose of
the radiation is approximately 10 mSv (millisievert), which is comparable with
the exposure to natural background radiation during approximately 3 years. This
exposure can slighly increase the risk of getting cancer. If the patient
cannot have a MRI scan, the research physician can choose for a CT-scan instead
of a MRI. In that case the research physician will be available to explain why
a CT-scan is more suitable than an MRI-scan and to answer potential questions
regarding the difference in risk between the two procedures.
Patients will be asked to come to the hospital at Screening, Baseline, Week 2,
4, 8, 12, 16, 20, 24 every 12 weken thereafter until progression of the
disease. The normal visits will take approxmately 30 minutes. For patients in
the Pacritinib arm and patients in the Best Available Therapy arm who went
cross-over to Pacritinib an additional ECG has to be performed 4 hours after
taking Pacritinib. at the Start of Week 1, 2 and 3 visits. The visits with a CT
or MRI (at Baseline and then every 12 weeks until progression) will take
approximately 1 hour.
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Seattle WA 98121
US
Listed location countries
Age
Inclusion criteria
1). Intermediate 1 or 2 or high-risk PMF, PPV-MF, or PET-MF (Passamonti et al 2010)
2). Palpable splenomegaly * 5 cm below LCM in midclavicular line by physical examination
3). Total Symptom Score (TSS) * 13 on the MPN-SAF-TSS2.0, not including te inactivity question.
4). Age * 18 years old
5). ECOG performance status 0-3
6). Peripheral blast count < 10%
7). Absolute neutrophil count > 500/*L
8). Patients who are platelet or red blood cell transfusion-dependent are eligible
9). Adequate liver and renal function, defined by liver transaminases (AST/SGOT and ALT/SGPT) * 3 × ULN (AST/ALT * 5 × ULN if transaminase elevation is related to MF), direct bilirubin * 4 x ULN, and creatinine * 2.5 mg/dL
10). At least 6 months from prior splenic irradiation
11). At least 12 months from prior 32P therapy
12). At least 1 week since prior treatment (most recent dose) with a potent CYP3A4 inhibitor
13). At least 4 weeks since any experimental treatment for PMF, PPV-MF, or PET-MF
14). At least 2 weeks since any treatment for PMF, PPV-MF, or PET-MF
15). If fertile, both males and females must agree to use effective birth control. Women of childbearing potential must use highly effective methods (defined as those resulting in a failure rate of <1% per year when used consistently and correctly) for the duration of study treatment and for 12 months after last dose of study drug. The contraceptive methods considered highly effective are intrauterine devices and hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections
with prolonged release).
16). Willingness to undergo and ability to tolerate frequent MRI or CT assessments on study
17). Ability to understand and willingness to complete symptom assessments using a patient reported outcomes instrument
18). Ability to understand and willingness to sign the informed consent form
Exclusion criteria
1). Any GI or metabolic condition that could interfere with absorption of oral medication
2). Life expectancy < 6 months
3). Prior treatment with a JAK2 inhibitor
4). Completed ASCT or eligible and willing to complete ASCT
5). History of splenectomy or planning to undergo splenectomy
6). Uncontrolled intercurrent illness, including but not limited to ongoing active infection or psychiatric illness or social situation that the treating physician judges would limit compliance with study requirements
7). Other malignancy within last 3 years other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with negative prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma
8). Inflammatory or chronic functional bowel disorder such as Crohn disease, inflammatory
bowel disease, chronic diarrhea, or constipation
9). Clinically symptomatic and uncontrolled cardiovascular disease
10). History of myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within 6 months prior to study randomization
11). New York Heart Association Class II, III, or IV congestive heart failure
12). Patients with CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, with approval of the medical monitor, if the arrhythmias are stable, aymptomatic and unlikely to affect patient safety. Ongoing cardiac dysrythmias of CTCAE * grade 3, corrected QTc prolongation > 450 ms or other factors that increase the risk for QT prolongation (eg, heart failure, serum potassium < 3.0 mEq/L, family history of long QT interval syndrome) are excluded.
13). Erythropoietic agent within 28 days prior to randomization
14). Thrombopoietic agent within 14 days prior to randomization
15). Known seropositivity for HIV
16). Known active hepatitis A, B, or C
17). Women who are pregnant or lactating
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 | EUCTR2012-004239-21-NL |
| CCMO | NL42821.029.12 |