Clinical Trial 23484

• Overview

  Study Title:

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

  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).

  Objective:

  Primary Objectives: To estimate the efficacy of reparixin treatment in DIPSS intermediate-2 or high-risk subjects with PMF, post PV-MF, or post ET-MF. Secondary Objectives: To assess the efficacy of reparixin as determined by response assessment using IWG/ELN criteria at the end of Cycle 6 and Cycle 12. To assess the change in bone marrow fibrosis grade at the end of Cycle 6 and Cycle 12 with reparixin. To assess the safety of reparixin as measured by the adverse event profile of CTCAE v5.0. To assess spleen volume reduction by imaging after cycles 6 and 12 as compared to baseline spleen volume.

• Treatments

  Therapies:

  Non-competitive allosteric inhibitor of CXCR1/2

  Medications:

  Reparixin ()

• Inclusion Criteria

  Inclusion Criteria:
  • Be at least 18 years of age at time of signing the ICF and 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 less than or equal to 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: (a) Treatment for ≥ 3 months with inadequate efficacy as demonstrated by persistent palpable splenomegaly ≥ 5cm or symptoms related to splenomegaly. (b) Treatment for greater than or equal to 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 > 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 outlined in protocol.
  • 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.

• Exclusion Criteria

  Exclusion Criteria:
  • 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: (a) 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 (b) 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 less than 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

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