Reparixin in Treating Patients with Primary Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, or Post-Polycythemia Vera Myelofibrosis
This phase II trial tests the side effects and how well reparixin works in treating patients with primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (post ET-MF), or post-polycythemia vera myelofibrosis (post PV-MF). Myelofibrosis is an uncommon type of blood cancer that affects the body’s normal production of blood cells. The production of blood cells normally occurs in the body’s bone marrow, however, in people with MF, the bone marrow is often scarred which leads to a lack of red blood cells which result in anemia, weakness, fatigue and an enlarged spleen. Reparixin is thought to block a protein called interleukin (IL)-8 which can affect the activation of white blood cells. Giving reparixin may induce changes in body’s immune system and may interfere with the ability of cancer cells to grow and spread.
Inclusion Criteria
- Be >= 18 years of age at time of signing the informed consent form (ICF)
- Able 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; 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 Janus kinase inhibitor (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) ** National Cancer Institute (NCI) CTCAE grade >= 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of < 20 mg twice daily (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
- Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) and/or aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 3x upper limit of normal (ULN), or =< 4 x ULN (if upon judgment of the treating physician, it is believed to be due to MF-related extramedullary hematopoiesis [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 10^9/L
- Bone marrow and peripheral blood blast count < 10%
- Absolute neutrophil count (ANC) >= 1000 mm^3
- 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 * WCBP is any woman (regardless of sexual orientation, having undergone a tubal litigation, or remaining celibate by choice) who meets the following criteria: ** Has not undergone a hysterectomy or bilateral oophorectomy; or ** Has not been naturally post-menopausal for at least 24 consecutive months if =< 55 years or 12 consecutive months if > 55 years * Adequate methods of contraception include use of: ** Single methods (one of the following is acceptable): *** Intrauterine device (IUD) *** Vasectomy of female subject’s male partner *** Contraceptive rod implanted into the skin ** Combination method (requires use of two of the following): *** Diaphragm with spermicide *** Cervical cap with spermicide (nulliparous women only) *** Contraceptive sponge (nulliparous women only) *** Male or female condom (cannot be used together) ** Hormonal contraceptive: oral contraceptive pill (estrogen/progestin or progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous contraceptive injection * Men must agree to use a condom and not father a child or donate sperm for the duration of the study and for 120 days after the last dose of study therapy
- Ability to adhere to the study visit schedule and all protocol requirements
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: * 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 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 Institutional Review Board (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
Additional locations may be listed on ClinicalTrials.gov for NCT05835466.
Locations matching your search criteria
United States
Florida
Tampa
New York
Buffalo
New York
North Carolina
Winston-Salem
PRIMARY OBJECTIVE:
I. To estimate the efficacy of reparixin treatment in Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or high-risk subjects with PMF, post PV-MF, or post ET-MF.
SECONDARY OBJECTIVES:
I. To assess the efficacy of reparixin as determined by response assessment using International Working Group (IWG)/European LeukemiaNet (ELN) criteria at the end of cycle 6 and cycle 12.
II. To assess the change in bone marrow fibrosis grade at the end of cycle 6 and cycle 12 with reparixin.
III. To assess the safety of reparixin as measured by the adverse event (AE) profile of Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
IV. To assess spleen volume reduction by imaging after cycles 6 and 12 as compared to baseline spleen volume.
EXPLORATORY OBJECTIVES:
I. To evaluate changes in quality of life (QOL) and patient-reported symptoms using the MF Symptom Assessment Form (MFSAF) version (v)4.0 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue/Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue in subjects treated with reparixin.
II. To assess Patient Global Impression of Change (PGIC).
III. To conduct correlative studies to measure biomarkers of reparixin activity, such as vascular endothelial growth factor (VEGF) levels, bone marrow microvessel density, megakaryocyte number and peripheral blood CD34+ cell number, and patients with and without IL-8 secretion.
OUTLINE:
Patients receive reparixin orally (PO) three times daily (TID) of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. If at least stable disease (SD) is met by IWG-MRT criteria, patients then receive reparixin PO once daily (QD) of each cycle. Cycles repeat every 28 days until loss of response, disease progression, unacceptable toxicity, patient/physician withdrawal, or termination of study by sponsor. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationIcahn School of Medicine at Mount Sinai
Principal InvestigatorMarina Kremyanskaya
- Primary ID22-2113
- Secondary IDsNCI-2023-05815
- ClinicalTrials.gov IDNCT05835466