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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type [Срок оценки: 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). [Срок оценки: 2 years]
• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by seriousness. [Срок оценки: 2 years]
• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by duration. [Срок оценки: 2 years]
• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by the relationship to study treatment. [Срок оценки: 2 years]

Вторичные конечные точки (6)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

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

Идентификаторы

NCT: NCT07521046 · HCI171996

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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