A Phase 3, Randomized, Double-blind, Active-Control Study of pelabresib (CPI0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAKi Treatment Naive MF Patients
- Conditions
- connective tissue proliferation in the bone marrowMyelofibrosis10024324
- Registration Number
- NL-OMON56000
- Lead Sponsor
- Constellation Pharmaceuticals, Inc.-A Morphosys Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 18
Patients are eligible to be included in the study only if all of the following
criteria apply:
Age
1. > or = 18 years of age at the time of signing the informed consent
Type of Patient and Disease Characteristics
2. Have a confirmed diagnosis of MF (PMF or PPV-MF or PET-MF) in accordance
with the 2016 WHO criteria (Section 10.4)
3. Require therapy for MF in the opinion of the Investigator and are eligible
for treatment with ruxolitinib
4. Have DIPSS risk category Intermediate-1 or higher (Section 10.5)
5. Have spleen volume of > or = 450 cm3 by MRI or CT scan (either local or
central read)
6. Have completed the MFSAF v4.0 (Section 10.6) at least 5 of 7 days prior to
randomization
7. Have at least 2 symptoms with an average score > or = 3 over the 7- day
period prior to randomization or an average total score of > or = 10 over the
7-day period prior to randomization using the MFSAF v4.0 (Section 10.6)
8. Have acceptable laboratory assessments obtained within 28 days prior to the
first dose of study medication:
• ANC > or = 1 × 109/L in the absence of growth factors or transfusions for the
previous 4 weeks
• Platelet count > or = 100 × 109/L in the absence of growth factors or
transfusions for the previous 4 weeks
• Peripheral blood blast count < 5%
• Isolated elevation of AST and ALT < or = 2.5 × ULN of the local reference
interval (< or = 5 × if the elevation can be ascribed to liver involvement;
e.g., presence of hepatomegaly)
• Isolated elevation of serum direct bilirubin < 2.0 × ULN of the local
reference interval
• Calculated or measured CrCl of > or = 45 mL/min *(equation used for
calculating CrCl will be captured in the eCRF)
9. ECOG performance status of < or = 2
10. Life expectancy > 24 weeks per Investigator assessment
11. Have fully recovered from major surgery, intervention, and from the
residual Grade 1 toxicity from prior MF-specific therapy (grade 1 peripheral
neuropathy and alopecia are allowed).
12. Both male and female patients and partners of patients and partners of
patients, with reproductive potential, must agree to use at least one highly
effective contraceptive method (preferably low user dependency contraception
methods, as in Section 6.9, in particular when contraception is introduced as a
result of participation in a clinical study) while on study therapy and for 94
days after the last dose of study drug for male patients and male partners of
female patients, and for 184 days after the last dose of study drug for female
patients and female partners of male patients. Patients of childbearing
potential are those who have not been
surgically sterilized or have not been free from menses for > 1 year. NOTE:
Patients may consider seeking information from the study investigator regarding
donation and cryopreservation of germ cells prior to treatment. Male patients
should be informed of the risk of testicular toxicity and provided with
adequate advice regarding sperm preservation.
13. Capable of giving signed informed consent as described in Section 10.1.3,
which includes compliance with the requirements and restrictions listed in the
ICF and in this protocol
1. Had splenic irradiation within 6 months of starting study drug
2. Had prior splenectomy
3. Are a candidate for, and willing to undergo allogeneic HSCT, and, in
the opinion of the Investigator, the benefit of proceeding to an
allogeneic HSCT prior to treatment with a JAK2 inhibitor outweighs its
risks
4. Have current known active or chronic infection with HIV, hepatitis B,
or hepatitis C. Screening of patients with serologic testing for these
viruses is not required. However, patients who have a past history of
viral hepatitis or in whom there is a current suspicion of viral hepatitis
should have serologic testing for hepatitis B and hepatitis C performed to
determine whether there is any current evidence for ongoing infection
with these viruses. Patients considered to be at risk for HIV infection
should have HIV testing performed.
5. Have an active infection. Patients will not be eligible for enrollment
until recovery to < or = Grade 1 for at least 2 weeks prior to the first
dose of study drug. Testing for COVID-19 is not mandatory during the screening
for this study. However, based on the local epidemiologic situation and each
patient*s individual COVID-19 exposure risk and/or vaccination status,
investigators should consider testing and in the case of COVID-19 positivity
consider delaying the start of the study treatment until the infection is
resolved.
6. Have impaired gastrointestinal function or gastrointestinal disease,
including active IBD, that could significantly alter the absorption of
study drug, including any unresolved nausea, vomiting, or diarrhea >
Grade 1
7. Have known hypersensitivity to the investigational agent or
ruxolitinib, or its metabolites or formulation excipients
8. Have a history of progressive multifocal leukoencephalopathy
9. Have impaired cardiac function or clinically significant cardiac
diseases, including any of the following:
• Acute myocardial infarction or unstable angina pectoris < or = 6
months prior to starting study drug
• QTcF > 500 msec on the screening ECG (QTcF interval is not relevant in
patients
with pacemaker-controlled arrythmia)
• New York Heart Association Class III or IV congestive heart failure
• Uncontrolled clinically significant cardiac arrhythmia (patients with
rate-controlled arrhythmias are not excluded)
-Patients with a history of coronary artery disease and revascularization
are not excluded.
10. Have ongoing uncontrolled hypertension (resting systolic blood
pressure >160 mmHg and resting diastolic blood pressure >100 mmHg)
despite maximal treatment with at least 2 anti-hypertensive agents
11. Have ongoing uncontrolled blood glucose increase (HbA1c > or =
9%) despite maximal treatment with oral and/or injectable antihyperglycemic
agents
12. Have a history of a concurrent or second malignancy except for
adequately treated local basal cell or squamous cell carcinoma of the
skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic
prostate cancer without known metastatic disease and with no
requirement for therapy or requiring only hormonal therapy and with
normal prostate-specific antigen for > or = 1 year prior to
randomization, adequately treated Stage 1 or 2 cancer currently in
complete remission, or any other cancer that has been in complete
remission for > or = 3 years
13. Have an
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary<br /><br>• Splenic response at Week 24</p><br>
- Secondary Outcome Measures
Name Time Method