Anemia, Myelodysplastic/Myeloproliferative Neoplasm, Myelofibrosis
Conditions
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.
Interventions
BIOLOGICALSotatercept
Given SC
DRUGRuxolitinib
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Monotherapy (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.
Sotatercept: Given SC | 35 |
| Treatment Combination (Ruxolitinib + 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.
Sotatercept: Given SC
Ruxolitinib | 21 |
| Total | 56 |
Baseline characteristics
| Characteristic | Treatment Combination (Ruxolitinib + Sotatercept) | Total | Treatment Monotherapy (Sotatercept) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 38 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 18 Participants | 14 Participants |
| Age, Continuous | 71 years | 67 years | 66 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) White | 14 Participants | 43 Participants | 29 Participants |
| Region of Enrollment United States | 21 participants | 56 participants | 35 participants |
| Sex: Female, Male Female | 7 Participants | 21 Participants | 14 Participants |
| Sex: Female, Male Male | 14 Participants | 35 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 21 |
| other Total, other adverse events | 30 / 35 | 19 / 21 |
| serious Total, serious adverse events | 11 / 35 | 10 / 21 |
Outcome results
Primary
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.
Time frame: Up to 84 days
Population: Of the 35 participants on the monotherapy arm, 27 were evaluable for response. Of the 21 participants on the Combination Therapy arm, 19 were evaluable for response.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Monotherapy (Sotatercept) | Anemia-response | 8 Participants |
| Treatment Combination (Ruxolitinib + Sotatercept) | Anemia-response | 6 Participants |
Primary
Duration of Response
Response date to loss of response or last follow up.
Time frame: Up to 9 years
Population: Of the 35 participants on the monotherapy arm, 27 were evaluable for response. Of the 21 participants on the Combination Therapy arm, 19 were evaluable for response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Monotherapy (Sotatercept) | Duration of Response | 23.3 Months |
| Treatment Combination (Ruxolitinib + Sotatercept) | Duration of Response | 19.9 Months |