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

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT01712308

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

111

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anemia Myelodysplastic/Myeloproliferative Neoplasm Myelofibrosis	Other: Laboratory Biomarker Analysis Biological: Sotatercept	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

Determine safety and efficacy of sotatercept as therapy for persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis and anemia.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 21, 2013

Actual Primary Completion Date :

May 24, 2022

Actual Study Completion Date :

May 24, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (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.	Other: Laboratory Biomarker Analysis Correlative studies Biological: Sotatercept Given SC Other Names: ACE-011 Decoy Activin Receptor ACE-011

Arm

Intervention/Treatment

Experimental: Treatment (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.

Other: Laboratory Biomarker Analysis

Correlative studies

Biological: Sotatercept

Given SC

Other Names:

ACE-011

Decoy Activin Receptor ACE-011

Outcome Measures

Primary Outcome Measures

Incidence of toxicities [Up to 28 days after the last dose of study drug]
Severity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Toxicity is defined as an adverse event and classified as possibly, probably, or definitely related to study drug. Such adverse events will be recorded by the principal investigator in a database. The maximum grade for each type of toxicity will be recorded for each patient, including start/stop dates, and frequency tables for each group will be reviewed to determine toxicity patterns.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)