RECRUITING

Reparixin in Patients with Myelofibrosis Myeloproliferative Neoplasms Research Consortium (MPN-RC 120)

Conditions

Myelofibrosis (PMF)Post Essential Thrombocythemia Myelofibrosis (ET-MF)Post Polycythemia Vera Related Myelofibrosis (PV-MF)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is an open label, phase II study to assess the efficacy, safety, and tolerability of Reparixin in patients with DIPSS intermediate-2, or high-risk primary myelofibrosis (PMF), post essential thrombocythemia/polycythemia vera related MF (Post ET/PV MF) after prior treatment, and those who are ineligible or refuse treatment, with a Janus kinase inhibitor (JAKi). 26 patients will be enrolled. Eligible patients will receive oral reparixin three times daily on a 4-week cycle for a core study period of 6 cycles (24 weeks). After cycle 6, patients may continue receiving reparixin once daily on a 4-week cycle if at least stable disease (SD) is met by IWG-MRT criteria until loss of response, disease progression, unacceptable toxicity, patient/physician withdrawal, or termination of study by sponsor.

Official Title

Phase II Study of Reparixin in Patients with Myelofibrosis Myeloproliferative Neoplasms Research Consortium [MPN-RC 120]

Quick Facts

Study Start:2023-07-24

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05835466

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Be ≥ 18 years of age at time of signing the ICF * Able to voluntarily sign the ICF * Have a pathologically confirmed diagnosis of PMF, post-ET-MF, or post-PV-MF as per the WHO diagnostic criteria with intermediate-2 or higher risk disease by DIPSS * Have an ECOG performance status ≤ 2 * Willing to undergo a bone marrow biopsy at screening; however, a bone marrow biopsy obtained within 90 days of screening without intervening treatments and approved by the study chair may suffice. * Be refractory/resistant to or intolerant of/inappropriate for JAKi therapy as defined by at least one of the following: * Treatment for ≥ 3 months with inadequate efficacy as demonstrated by persistent palpable splenomegaly ≥ 5cm or symptoms related to splenomegaly. * Treatment for ≥ 28 days complicated by either: * Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months) * NCI CTCAE grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of \< 20 mg BID * In the Investigator's judgment, are not candidates for available approved JAKi * Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia * At least two weeks must have elapsed between the last dose of any MF-directed drug treatments (including investigational therapies and excluding hydroxyurea) and study enrollment * Have adequate organ function as demonstrated by the following: * ALT (SGPT) and/or AST (SGOT) ≤ 3x ULN, or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to MF-related EMH); * Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to MF-related EMH or documented Gilbert's syndrome); * Creatinine clearance ≥ 40 mL/min ; * Platelet count ≥ 25 x 109/L; * Bone marrow and peripheral blood blast count \< 10%; * ANC ≥ 1000 mm3. * Life expectancy of at least six months * Women of childbearing potential (WCBP) and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 120 days following completion of therapy. WCBP must also have a negative serum pregnancy test at screening and Cycle 1 Day 1. Should a woman become pregnant or suspect she is pregnant while participating, she should inform her treating physician immediately. * Ability to adhere to the study visit schedule and all protocol requirements.	* Use of an investigational agent or an investigational device within 4 weeks of the first dose of study therapy * History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months * Other invasive malignancies within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer * Moderate or severe cardiovascular disease meeting one or both of the below criteria: * Presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension * Documented major ECG abnormalities (not responding to medical treatments) * Presence of active serious infection * Any serious, unstable medical or psychiatric condition that would prevent (as judged by the Investigator) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study * Participants who have undergone a hematopoietic cell transplant (HCT) within 100 days of the first dose of study therapy, participants on immunosuppressive therapy post-HCT at screening, use of calcineurin inhibitors within 4 weeks prior to first dose of study therapy, or participants with clinically significant graft-versus-host disease (GVHD) * Note: The use of topical steroids or \< 10mg oral prednisone for ongoing skin GVHD is permitted * Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection * Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of reparixin, including any unresolved nausea, vomiting, or diarrhea \> CTCAE grade 1 * Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject * Organ transplant recipients other than bone marrow transplant * Women who are pregnant or lactating

Inclusion Criteria

Exclusion Criteria

* Be ≥ 18 years of age at time of signing the ICF
* Able to voluntarily sign the ICF
* Have a pathologically confirmed diagnosis of PMF, post-ET-MF, or post-PV-MF as per the WHO diagnostic criteria with intermediate-2 or higher risk disease by DIPSS
* Have an ECOG performance status ≤ 2
* Willing to undergo a bone marrow biopsy at screening; however, a bone marrow biopsy obtained within 90 days of screening without intervening treatments and approved by the study chair may suffice.
* Be refractory/resistant to or intolerant of/inappropriate for JAKi therapy as defined by at least one of the following:
* Treatment for ≥ 3 months with inadequate efficacy as demonstrated by persistent palpable splenomegaly ≥ 5cm or symptoms related to splenomegaly.
* Treatment for ≥ 28 days complicated by either:
* Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months)
* NCI CTCAE grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of \< 20 mg BID
* In the Investigator's judgment, are not candidates for available approved JAKi
* Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia
* At least two weeks must have elapsed between the last dose of any MF-directed drug treatments (including investigational therapies and excluding hydroxyurea) and study enrollment
* Have adequate organ function as demonstrated by the following:
* ALT (SGPT) and/or AST (SGOT) ≤ 3x ULN, or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to MF-related EMH);
* Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to MF-related EMH or documented Gilbert's syndrome);
* Creatinine clearance ≥ 40 mL/min ;
* Platelet count ≥ 25 x 109/L;
* Bone marrow and peripheral blood blast count \< 10%;
* ANC ≥ 1000 mm3.
* Life expectancy of at least six months
* Women of childbearing potential (WCBP) and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 120 days following completion of therapy. WCBP must also have a negative serum pregnancy test at screening and Cycle 1 Day 1. Should a woman become pregnant or suspect she is pregnant while participating, she should inform her treating physician immediately.
* Ability to adhere to the study visit schedule and all protocol requirements.

* Use of an investigational agent or an investigational device within 4 weeks of the first dose of study therapy
* History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
* Other invasive malignancies within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer
* Moderate or severe cardiovascular disease meeting one or both of the below criteria:
* Presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension
* Documented major ECG abnormalities (not responding to medical treatments)
* Presence of active serious infection
* Any serious, unstable medical or psychiatric condition that would prevent (as judged by the Investigator) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
* Participants who have undergone a hematopoietic cell transplant (HCT) within 100 days of the first dose of study therapy, participants on immunosuppressive therapy post-HCT at screening, use of calcineurin inhibitors within 4 weeks prior to first dose of study therapy, or participants with clinically significant graft-versus-host disease (GVHD)
* Note: The use of topical steroids or \< 10mg oral prednisone for ongoing skin GVHD is permitted
* Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection
* Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of reparixin, including any unresolved nausea, vomiting, or diarrhea \> CTCAE grade 1
* Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject
* Organ transplant recipients other than bone marrow transplant
* Women who are pregnant or lactating

Contacts and Locations

Study Contact

Ashley Yu, MBA

CONTACT

(347) 802-7000

ashley.yu@mssm.edu

Principal Investigator

Marina Kremyanskaya, PhD, MD

STUDY_CHAIR

Icahn School of Medicine at Mount Sinai

Aaron Gerds, MD, MS

STUDY_CHAIR

Cleveland Clinic Taussig Cancer Institute

Study Locations (Sites)

Roswell Park Cancer Institute

Buffalo, New York, 14263

United States

Ruttenberg Treatment Center

New York, New York, 10029

United States

Wake Forest Baptist Health Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157

United States

Collaborators and Investigators

Sponsor: Icahn School of Medicine at Mount Sinai

Marina Kremyanskaya, PhD, MD, STUDY_CHAIR, Icahn School of Medicine at Mount Sinai
Aaron Gerds, MD, MS, STUDY_CHAIR, Cleveland Clinic Taussig Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-24

Study Completion Date2027-12

Study Record Updates

Study Start Date2023-07-24

Study Completion Date2027-12

Terms related to this study

Additional Relevant MeSH Terms

Myelofibrosis (PMF)
Post Essential Thrombocythemia Myelofibrosis (ET-MF)
Post Polycythemia Vera Related Myelofibrosis (PV-MF)