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

Phase 2

Completed

Conditions: Anemia
Myelodysplastic/Myeloproliferative Neoplasm
Myelofibrosis

Interventions: Biological: Sotatercept
Drug: Ruxolitinib

Registration Number: NCT01712308

Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 56

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Monotherapy (sotatercept)	Sotatercept	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.
Treatment combination (Ruxolitinib + sotatercept)	Sotatercept	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.
Treatment combination (Ruxolitinib + sotatercept)	Ruxolitinib	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.

Primary Outcome Measures

Name	Time	Method
Anemia-response	Up to 84 days	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.
Duration of Response	Up to 9 years	Response date to loss of response or last follow up.

Secondary Outcome Measures