OPEN Clinical Trials

MPN-RC 120

ClinicalTrials.gov Clinical Trial 120 Listing

Phase II Study of Reparixin in Patients with Myelofibrosis Myeloproliferative Neoplasms Research Consortium

Study Status: Active 

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).
This study will use a Bayesian optimal phase 2 (BOP2) design with interim stopping boundaries for toxicity/efficacy. Eligible patients will receive oral reparixin once 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.

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.

Inclusion Criteria

1. Be ≥ 18 years of age at time of signing the ICF

2. Able to voluntarily sign the ICF

3. 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

4. Have an ECOG performance status ≤ 2

5. 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.

6. Be refractory/resistant to or intolerant of/inappropriate for JAKi therapy as defined by at least one of the following:
1. Treatment for ≥ 3 months with inadequate efficacy as demonstrated by persistent palpable splenomegaly ≥ 5cm or symptoms related to splenomegaly.
2. Treatment for ≥ 28 days complicated by either:
     2.1. Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months)
     2.2. NCI CTCAE grade ≥ 3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of < 20 mg BID
     3. In the Investigator’s judgment, are not candidates for available approved JAKi

7. Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia

8. 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

9. Have adequate organ function as demonstrated by the following:
    9.1. 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);
   9.2. 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);
   9.3. Creatinine clearance ≥ 40 mL/min ;
   9.4. Platelet count ≥ 25 x 109/L;
   9.5. Bone marrow and peripheral blood blast count < 10%;
   9.6. ANC ≥ 1000 mm3.

10. Life expectancy of at least six months

11. 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.

12. Ability to adhere to the study visit schedule and all protocol requirements

Exclusion Criteria

1. Use of an investigational agent or an investigational device within 4 weeks of the first dose of study therapy

2. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months

3. Other invasive malignancies within the last 3 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer

4. Moderate or severe cardiovascular disease meeting one or both of the below criteria:
    1.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
    2.Documented major ECG abnormalities (not responding to medical treatments)

5. Presence of active serious infection

6. 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

7. 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)
   1.Note: The use of topical steroids or < 10mg oral prednisone for ongoing skin GVHD is permitted

8. Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection

9. 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

10. 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

11. Organ transplant recipients other than bone marrow transplant

12. Women who are pregnant or lactating

MPN-RC 122

ClinicalTrials.gov Clinical Trial 122 Listing

A Phase 2 study of Canakinumab in patients with Myelofibrosis Myeloproliferative Neoplasms Research Consortium

Study Status: Active

MPN-RC 122 Summary:

This is an open label, phase 2 study to assess the efficacy, safety, and tolerability of Canakinumab in patients with primary myelofibrosis (PMF), post essential thrombocythemia/polycythemia vera related MF (Post ET/PV MF) after prior treatment, and those who are not appropriate for JAK inhibitor therapy.

Primary Objective: To estimate the efficacy of Canakinumab treatment in patients with PMF, post PV-MF, or post ET-MF. The primary objective of this study is to evaluate efficacy of Canakinumab in patients with MF by the end of 8 cycles (24 weeks) based on IWG-MRT critieria.42 A response is considered any one of the following: complete response, partial response, or clinical improvement (inclusive of anemia response, spleen response, or symptom response).

Inclusion Criteria:

1. Patients must voluntarily sign informed consent form (ICF) and be willing and able to adhere to the study visit schedule and all protocol requirements.

2. Patients must be ≥ 18 years of age at the time of signing the ICF.

3. Patients must have a pathologically confirmed diagnosis of primary myelofibrosis (PMF) as per the World Health Organization (WHO) diagnostic criteria44 or post-essential thrombocythemia (ET) / post-polycythemia vera (PV) MF according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria.45

4. Patients must have at least one of the following:
    a. Hemoglobin < 10 g/dL
    b. Transfusion-dependency (at least 6 units of packed red blood cells (PRBC) in the 12 weeks prior to study enrollment, for a hemoglobin < 8.5 g/dL, in the absence of bleeding or treatment-induced anemia with the most recent transfusion having occurred in the 28 days prior to study enrollment.
   c. Splenomegaly palpated ≥ 5 cm below the left costal margin (LCM)
   d. MF-SAF version 4.0 score ≥ 10

5. A bone marrow biopsy must be performed within the 30-day screening period; however, a bone marrow biopsy obtained within 90 days of signing ICF without intervening treatments and approved by the study chair may suffice.
6. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

7. Life expectancy of at least 6 months.

8. 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.

9. Not eligible for ruxolitinib/fedratinib therapy due to a platelet count of < 50 x 109/L or previously treated and lack/loss of response per investigator discretion.

10. Recovery to ≤ grade 1 or baseline of any toxicities due to prior systemic treatments excluding alopecia.

11. Women of childbearing potential (WCBP) must have a negative urine or serum pregnancy test within 28 days of starting the study drug. Men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence, tubal ligation, vasectomy) prior to cycle 1 day 1 and for 130 days after stopping study treatment. Vasectomy must be performed a minimum of 3 months before study start.

12. Must have adequate organ function as demonstrated by the following:
   a. ALT/AST ≤ 3.0X ULN, or ≤ 4X ULN (unless if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis (EMH) related to MF);
   b. Direct bilirubin ≤ 1.5 x ULN or ≤ 2.0 x ULN (unless if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis related to MF or documented Gilbert’s syndrome);
   c. Serum creatinine ≤ 2.0 mg/dL;
   d. Platelet count ≥ 25 x 109/L (patient must not have had platelet transfusion in the 14 days prior to signing ICF);
   e. ANC ≥ 1000/μL

13. Patient must be willing to receive red blood cell and/or platelet transfusions if indicated.

Exclusion Criteria:

Prior malignancy active within the previous ≤1 year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

1. Any of the following cardiac abnormalities
   a. Uncontrolled, symptomatic congestive heart failure as designated by the treating physician
   b. Myocardial infarction ≤ 6 months prior to enrollment
   c. Unstable angina pectoris designated by treating physician
   d. Serious uncontrolled cardiac arrhythmia as designated by treating physician
   e. Uncontrolled hypertension as designated by treating physician

2. Known history of human immunodeficiency virus (HIV) (no laboratory testing is required), or active infection with hepatitis B or Hepatitis C.

3. Active tuberculosis (Tb) infection or documented, untreated latent Tb infection (all patients should undergo Tb risk evaluation prior to enrollment with Tb screening performed as per local guidelines.)
4. Active, uncontrolled infection at the time of enrollment, except in cases of localized infections that are unlikely to lead to a systemic infection such as onychomycoses or dental caries. a. Patients with a new fever (T>38.0o C) or respiratory symptoms are required to undergo laboratory screening for COVID-19.

5. Have undergone prior allo-HSCT for treatment of any hematological disorder or prior solid organ transplant.

6. Any serious or uncontrolled psychiatric or medical disorder that, in the opinion of the investigator, may increase the risk associated with the study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.

7. Women who are pregnant or breastfeeding.

8. Patients undergoing concurrent treatment with agents targeting tumor necrosis factor alpha (TNFα) or IL-1 within 28 days of study enrollment.

9. Patients who have received a live vaccination within 30 days before study drug administration (patients should not be treated with live-virus vaccine while undergoing therapy and 130 days after Canakinumab discontinuation).

10. Patients with a condition requiring systemic treatment with corticosteroids within 14 days of study drug administration (i.e. prednisone at doses of > 10 mg). Inhaled or topical steroids and adrenal/pituitary replacement doses ≤ 10mg daily of prednisone or equivalent are permitted.