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Back|NCT05835466Recruiting
Official Title

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

Phase
Phase 2
Sponsor
Icahn School of Medicine at Mount Sinai
Enrollment
26
Timeline
Jul 2023 → Dec 2028
About This Study

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.

Eligibility Criteria

Inclusion Criteria

  • 1Be ≥ 18 years of age at time of signing the ICF
  • 2Able to voluntarily sign the ICF
  • 3Have 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
  • 4Have an ECOG performance status ≤ 2
  • 5Willing 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.
  • 6Be refractory/resistant to or intolerant of/inappropriate for JAKi therapy as defined by at least one of the following:
  • 7Treatment for ≥ 3 months with inadequate efficacy as demonstrated by persistent palpable splenomegaly ≥ 5cm or symptoms related to splenomegaly.
  • 8Treatment for ≥ 28 days complicated by either:
  • 9Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months)
  • 10NCI CTCAE grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of \< 20 mg BID
  • 11In the Investigator's judgment, are not candidates for available approved JAKi
  • 12Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia
  • 13At 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
  • 14Have adequate organ function as demonstrated by the following:
  • 15ALT (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);
  • 16Direct 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);
  • 17Creatinine clearance ≥ 40 mL/min ;
  • 18Platelet count ≥ 25 x 109/L;
  • 19Bone marrow and peripheral blood blast count \< 10%;
  • 20ANC ≥ 1000 mm3.
  • 21Life expectancy of at least six months
  • 22Women 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.
  • 23Ability to adhere to the study visit schedule and all protocol requirements.

Exclusion Criteria

  • 1Use of an investigational agent or an investigational device within 4 weeks of the first dose of study therapy
  • 2History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
  • 3Other invasive malignancies within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer
  • 4Moderate or severe cardiovascular disease meeting one or both of the below criteria:
  • 5Presence 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
  • 6Documented major ECG abnormalities (not responding to medical treatments)
  • 7Presence of active serious infection
  • 8Any 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
  • 9Participants 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)
  • 10Note: The use of topical steroids or \< 10mg oral prednisone for ongoing skin GVHD is permitted
  • 11Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection
  • 12Impairment 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
  • 13Is 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
  • 14Organ transplant recipients other than bone marrow transplant
  • 15Women who are pregnant or lactating

Locations

9 sites participating in this study

Emory University

Atlanta, Georgia 30322

Recruiting

Anthony Hunter, MD

Moffitt Cancer Center

Tampa, Florida 33612

Recruiting

Andrew Kuykendall, MD

Roswell Park Cancer Institute

Buffalo, New York 14263

Recruiting

Eunice Wang, MD

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →