Sotatercept in Treating Patients With Myeloproliferative Neoplasm-Associated Myelofibrosis or Anemia

Study Overview
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Brief Summary
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This phase II trial studies the side effects of and how well sotatercept works in treating patients with myeloproliferative neoplasm-associated myelofibrosis or anemia. Sotatercept may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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The goal of this clinical research study is to learn if sotatercept can help to control MPN-associated myelofibrosis and anemia. The safety of this drug will also be studied. OUTLINE: This is a dose-escalation study. Patients receive sotatercept subcutaneously (SC) once every 3 weeks. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients unable to achieve anemia-response after 8 cycles will be taken off study. After completion of study treatment, patients are followed up at 1 month.

Official Title
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A Phase-2, Prospective, Open-Label Study to Determine the Safety and Efficacy of Sotatercept (ACE-011) in Subjects With Myeloproliferative Neoplasm (MPN) -Associated Myelofibrosis and Anemia

Conditions
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Anemia, Myelodysplastic/Myeloproliferative Neoplasm, Myelofibrosis

Intervention / Treatment
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* Biological: Sotatercept
* Drug: Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MPN-associated myelofibrosis Anemic patient OR red blood cell (RBC)-transfusion-dependent patient Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) equal to or less than 2.5 x upper limit of normal (ULN), or equal to or less than 4 x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to myelofibrosis [MF]) Direct bilirubin equal to or less than 1.5 x ULN; or equal to or less than 2 x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis related to MF) Creatinine clearance equal to or more than 50 mL/min Treatment-related toxicities from prior therapies must have resolved to grade equal to or less than 1 Women of childbearing potential and men must agree to using medically approved (i.e., mechanical or pharmacological) contraceptive measure for at least 112 days following the last dose of sotatercept (ACE-011); males must agree to use a latex condom or non-latex condom NOT made of natural (animal) membrane during any sexual contact with females of childbearing potential or a pregnant female while participating in the study and for at least 112 days following the last dose of sotatercept (ACE-011), even if he has a vasectomy For cohort of patients that are already on ruxolitinib therapy: on therapy with ruxolitinib for at least for 6 months, and on stable dose for last 2 months, before starting therapy with sotatercept Exclusion Criteria: Serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) 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 Pregnant or lactating female Known positive for human immunodeficiency virus-1 (HIV-1), or active infection with hepatitis-B or -C Use of any MPN-associated myelofibrosis-directed therapy within 2 weeks prior to study day 1 (other than ruxolitinib at a stable dose for patients in the combination cohort as stated in inclusion criteria) Symptomatic congestive heart failure, unstable angina, or unstable cardiac arrhythmia Prior sotatercept Major surgery within 4 weeks prior to day 1 Severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product Uncontrolled hypertension (systolic blood pressure [SBP] equal to or more than 140 or diastolic blood pressure [DBP] equal to or more than 90)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Monotherapy (sotatercept)<br>Patients receive sotatercept SC once every 3 weeks. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients unable to achieve anemia-response after 8 cycles will be taken off study. | Biological: Sotatercept<br>* Given SC<br>* Other names: Decoy Activin Receptor ACE-011;|
| Experimental: Treatment combination (Ruxolitinib + sotatercept)<br>patients that are already on therapy with ruxolitinib (for at least for 6 months, and on stable dose for last 2 months) will continue ruxolitinib in addition to sotatercept SC once every 3 weeks. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients unable to achieve anemia-response after 8 cycles will be taken off study. | Biological: Sotatercept<br>* Given SC<br>* Other names: Decoy Activin Receptor ACE-011;Drug: Ruxolitinib<br> <br> * Other names: INCB018424;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anemia-response | Defined as an increase in hemoglobin level equal to or greater than 1.5 g/L without red blood cell-transfusion OR becoming red blood cell-transfusion-independent in a patient who is red blood cell-transfusion-dependent. Will be based on the intent-to-treat principle. | Up to 84 days | 
| Duration of Response | Response date to loss of response or last follow up. | Up to 9 years |