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

NCT05835466 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY-22-01764
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Efficacy of reparixin treatment per IWG/ELN criteria

  To estimate the efficacy of reparixin treatment in DIPSS intermediate-2 or high-risk subjects with PMF, post PV-MF, or post ET-MF as assessed by IWG/ELN criteria. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission

  Cycle 6 (each cycle is 4 weeks) Response Assessment

Secondary Outcomes (7)

• Response Assessment of IWG/ELN

  end of Cycle 6 (each cycle is 4 weeks)

• Response Assessment of IWG/ELN

  end of Cycle 12 (each cycle is 4 weeks)

• Bone marrow fibrosis grade

  end of Cycle 6 (each cycle is 4 weeks)

• Bone marrow fibrosis grade

  end of Cycle 12 (each cycle is 4 weeks)

• Number of Adverse Events

  End of study (24 weeks) plus 3 months

Study Arms (1)

Reparixin

EXPERIMENTAL

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.

Drug: reparixin

Interventions

reparixin DRUG

reparixin at 1200mg TID three times per day.

Reparixin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be ≥ 18 years of age at time of signing the informed consent form (ICF)
• Willing to voluntarily sign the ICF
• Have a pathologically confirmed diagnosis of PMF, post-ET-MF, or post-PV-MF as per the World Health Organization (WHO) diagnostic criteria with intermediate-2 or higher risk disease by DIPSS
• Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Willing to undergo a bone marrow biopsy at screening
• o 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)
• CTCAE grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, or hemorrhage while being treated with a JAKi
• Development of non-hematological toxicity that makes patient intolerant of JAKi therapy
• 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 or other investigational therapies and start of reparixin

You may not qualify if:

• 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 electrocardiogram (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 participant from signing the ICF or any condition, including the presence of laboratory abnormalities, which places the participant 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)
• o 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 institutional review board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific participant
• Organ transplant recipients other than bone marrow transplant
• Women who are pregnant or lactating
• History of splenectomy

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: collaborator
• Icahn School of Medicine at Mount Sinai: lead

Study Sites (9)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Ruttenberg Treatment Center

New York, New York, 10029, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

NewYork-Presbyterian/Weill Cornell Medical Center

New York, New York, 10065, United States

RECRUITING

Wake Forest Baptist Health Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

reparixin

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Marina Kremyanskaya, PhD, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

• Aaron Gerds, MD, MS

  Cleveland Clinic Taussig Cancer Institute

  STUDY CHAIR

Central Study Contacts

Gillian Sanchez

CONTACT

(917) 581-1774; gillian.sanchez@mssm.edu

Shakira Forde

CONTACT

212-824-8334; shakira.forde@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 28, 2023
• Study Start: July 24, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)