Myelofibrosis is commonly treated with a drug called Ruxolitinib. Since Ruxolitinib is approved, it is usually your doctor’s first choice of treatment.This study is being done to find out if taking Ruxolitinib and the study medication, Pelabresib (CPI-0610), together work better than taking only Ruxolitinib, and if it can help decrease your spleen size and make you feel better. To be part of this study, you may not have taken Ruxolitinib before.

Phase 1

Active, not recruiting

• Conditions: Myelofibrosis; MedDRA version: 20.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10074689Term: Post polycythemia vera myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 21.0Level: LLTClassification code 10074690Term: Post essential thrombocythemia myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10077161Term: Primary myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2020-001989-10-AT
• Lead Sponsor: Constellation Pharmaceuticals, Inc. A MorphoSys Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-09
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

Patients are eligible to be included in the study only if all of the following criteria apply:
Age
1. = 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 = 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 = 3 over the 7-day period prior to randomization or an average total score of = 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 = 1 × 109/L in the absence of growth factors or transfusions for the previous 4 weeks
• Platelet count = 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/or ALT = 2.5 × ULN of the local reference interval(= 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 = 45 mL/min
9. ECOG performance status of = 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, 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
*Equation used for calculating the estimated creatinine clearance will be
captured in the eCRF.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion Criteria

Exclusion criteria 1.-4. did not change. Please see protocol section 5.2.
page 27.
5. Have an active infection. Patients will not be eligible for enrollment
until recovery to = 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 = 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)
Note that 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/uncontrolled
diabetes (HbA1c =9%) despite maximal treatment with oral and/or
injectable anti-hyperglycemic 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 = 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 = 3 years
13. Have any other concurrent severe and/or uncontrolled concomitant
medical condition that in the opinion of the Investigator could
compromise participation in the study or analysis of study data. This
includes but is not limited to clinically significant pulmonary disease or
neurological disorders.
Prior/Concomitant Therapy
14. Had prior treatment with any JAKi or BET inhibitor for treatment of
a myeloproliferative neoplasm
15. Had systemic anti-cancer treatment, with the exception of hormonal
therapy, less than 2 weeks (or 5 half-lives, whichever is longer) before
the first dose of study drug. NOTE: Hydroxyurea and anagrelide are
permitted up to 24 hours prior to start of study drug. Consult the
Medical Monitor with questions if needed.
16. Had any investigational agent (whether as cancer treatment or not)
less than 2 weeks (or 5 half-lives, whichever is longer) before the first
dose of study drug.
17. Had hematopoietic growth f

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified