Tolerability of Ropeginterferon Alfa-2b Add-on to Ongoing Ruxolitinib Therapy in Myelofibrosis (RopeRux in Myelofibrosis)

Official title

A Phase 1b Study of Safety, Tolerability of Ropeginterferon Alfa-2b Add-on to Ongoing Ruxolitinib Therapy in Myelofibrosis (RopeRux in Myelofibrosis)

Overview

The purpose of this clinical trial is to learn if the study drug ropeginterferon alfa- 2b added to, standard of care, ruxolitinib is safe and effective in treating patients with Myelofibrosis.

Interventions

• Drug ropeginterferon alfa- 2b
  Ropeginterferon alfa- 2b will be administered as a subcutaneous injection every two weeks.
• Drug Ruxolitinib
  Ruxolitinib will be administered per standard of care.

Primary outcome measures

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type [Time frame: 2 years]
• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by severity (as defined by the NIH CTCAE, version 6.0). [Time frame: 2 years]
• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by seriousness. [Time frame: 2 years]
• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by duration. [Time frame: 2 years]
• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by the relationship to study treatment. [Time frame: 2 years]

Secondary outcome measures (6)

• The proportion of subjects who achieve >50% reduction in JAK2 V617F mutation burden. [Time frame: 2 years]
• Change in JAK2, CALR, MPL mutations allelic burden. [Time frame: 2 years]
• The proportion of subjects who achieve a 25% decrease in spleen volume by 24 weeks from initiation of combination treatment. [Time frame: 24 weeks]
• Change in quality of life Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) from baseline and throughout treatment. [Time frame: 2 years]
• The proportion of subjects who progress to blastic phase and secondary acute myeloid leukemia at 2 years post-treatment. [Time frame: 2 years]
• The proportion of subjects who have a change in bone marrow fibrosis grade. [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Male or female subject aged ≥ 18 years.
• Diagnosed with PMF, post-PV MF, or post-ET MF per WHO 2016 or 2022 criteria, bearing one of these MPN phenotype defining mutations (JAK2, CALR, and MPL), and with a DIPSS score of low, intermediate-1 or intermediate-2.
• Subjects must be already on standard of care ruxolitinib per the treating physician for at least 3 months or more, and on a stable dose for at least 6 weeks prior to screening.
• Subjects must have spleen volume of > 450ml by either MRI or CT scan
• Subject must have a JAK2, CALR, or MPL allelic burden of ≥20% at screening

--Prior treatment for PV or ET with hydroxyurea or ruxolitinib is allowed. If the patient was on pegylated interferon in the past, the progression from PV/ ET to post-PV/ET MF must not have occurred while on pegylated interferon therapy.

• ECOG Performance Status ≤ 2.
• Adequate organ function as defined as:

• Hematologic:

• WBC count ≥ 4 x 109/L
• Absolute neutrophil count (ANC) ≥1500/mm3
• Platelet count ≥ 75,000/mm3
• Hemoglobin ≥ 8 g/dL
• Hepatic:

---Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)

---AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN

• Renal:

• Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula
• Recovery to baseline or ≤ Grade 1 CTCAE v 6.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy per the treating investigator.
• Participants must adhere to the following sex and contraceptive/barrier requirements:

• If participant is of childbearing potential, they must have a negative pregnancy test
• For participants of non-childbearing potential: The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• < 50 years of age:

---Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and

---Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution

--≥ 50 years of age:

---Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or

---Had radiation-induced menopause with last menses >1 year ago; or

---Had chemotherapy-induced menopause with last menses >1 year ago

---Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution

• Participants of childbearing potential and participants with a sexual partner of childbearing potential must agree to use a highly effective method of contraception and lactation requirements as described in Sections 6.4.1 and 6.4.3.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion criteria

• PV or ET patients who progressed while on pegylated interferon or ropeginterferon therapy.
• Receiving other investigational agents.
• Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt (Patients with pre-existing depression who are well-controlled and on stable doses of antidepressants are eligible).
• Evidence of severe retinopathy or clinically significant eye disease.
• History or presence of active serious or untreated autoimmune disease.
• History of solid organ transplant.
• Liver cirrhosis Child-Pugh score B or C. -≥ 5% blasts in peripheral blood or bone marrow.
• Prior systemic anti-cancer therapy or any investigational therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter.
• Major surgery 4 weeks prior to starting study drug or who have not fully recovered from major surgery.
• The diagnosis of another malignancy which, in the investigator's opinion, is likely to significantly impact study participation.
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:

• Cardiovascular disorders:

• Uncontrolled hypertension, in the opinion of the investigator
• Congestive heart failure New York Heart Association Class II or greater, unstable angina pectoris, serious cardiac arrhythmias.
• Stroke or myocardial infarction within the past 3 months
• Significant coronary stenosis, in the opinion of the investigator
• QTc prolongation defined as a QTcF > 500 ms.
• Known congenital long QT.
• Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/ psychological issues, etc.)
• Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.

Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.

-Active infection requiring systemic therapy, including, but not limited to: tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C.

Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

• Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
• Known prior severe hypersensitivity to investigational product (IP) or any component in its formulations (NCI CTCAE v 6.0 Grade ≥ 3).
• Subjects taking prohibited medications as described in Section 7.8. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Huntsman Cancer Institute at University of Utah — Salt Lake City

Identifiers

NCT: NCT07521046 · HCI171996

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗