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

Primary Purpose

Anemia, Myelodysplastic/Myeloproliferative Neoplasm, Myelofibrosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sotatercept
Ruxolitinib
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Treatment Monotherapy (sotatercept)

Treatment combination (Ruxolitinib + sotatercept)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
Duration of Response
Response date to loss of response or last follow up.

Secondary Outcome Measures

Full Information

First Posted
October 18, 2012
Last Updated
October 2, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01712308
Brief Title
Sotatercept in Treating Patients With Myeloproliferative Neoplasm-Associated Myelofibrosis or Anemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
February 21, 2013 (Actual)
Primary Completion Date
May 24, 2022 (Actual)
Study Completion Date
May 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Myelodysplastic/Myeloproliferative Neoplasm, Myelofibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Monotherapy (sotatercept)
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment combination (Ruxolitinib + sotatercept)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Sotatercept
Other Intervention Name(s)
ACE-011, Decoy Activin Receptor ACE-011
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
INCB018424
Primary Outcome Measure Information:
Title
Anemia-response
Description
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.
Time Frame
Up to 84 days
Title
Duration of Response
Description
Response date to loss of response or last follow up.
Time Frame
Up to 9 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prithviraj Bose
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

Learn more about this trial

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

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