Myelodysplastic Syndromes (MDS) MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: HLT Classification code 10028536 Term: Myelodysplastic syndromes System Organ Class: 100000004851
Conditions
Sponsors
Acceleron Pharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All patients must meet the following criteria: 1. Completion of the treatment period in the base study A536-03. 2. Females of child bearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy, or are not naturally postmenopausal = 24 consecutive months) must have negative urine or blood pregnancy test prior to enrollment and use adequate birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 12 weeks following the last dose of ACE-536. Males must agree to use a latex condom during any sexual contact with females of child-bearing potential while participating in the study and for 12 weeks following the last dose of ACE-536, even if he has undergone a successful vasectomy. Patients must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to dosing with ACE-536. 3. Patient is able to adhere to the study visit schedule, understand and comply with all protocol requirements. 4. Patient understands and is able to provide written informed consent. Patients with treatment interruption (defined as patients who complete their A536-03 EOS visit) must also meet the following criteria: 1. Documented diagnosis of idiopathic/de novo MDS or non-proliferative chronic myelomonocytic leukemia (CMML) according to the World Health Organization (WHO) criteria2 (white blood count [WBC] =65 years) yes F.1.3.1 Number of subjects for this age range 77
Exclusion criteria
Exclusion criteria: 1. Discontinuation/withdrawal from the base study A536-03 (due to patient request, patient unwillingness or inability to comply with the protocol, pregnancy, use of prohibited medication [e.g. azacitidine], medical reason or AE, disease progression, persistent increase in white blood cell count (WBC), presence of = 1% blasts in peripheral blood, hypersensitivity reaction to the study drug, at the discretion of the sponsor, or loss to follow-up) prior to completion of the treatment period. 2. Prior treatment with azacitidine (injectable or oral) or decitabine. 3. Treatment within 28 days prior to Cycle 1 Day 1 with: - ESA, - Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF), - Lenalidomide. 4. For patients with treatment interruption only: Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1. 5. Treatment with another investigational drug (including sotatercept [ACE-011]) or device, or approved therapy for investigational use = 28 days prior to Cycle 1 Day 1, or if the half-life of the previous investigational product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer. 6. Major surgery within 28 days prior to Cycle 1 Day 1. Patients must have completely recovered from any previous surgery prior to Cycle 1 Day 1. 7. Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV). 8. Uncontrolled hypertension defined as systolic blood pressure (SBP) = 150 mm Hg or diastolic blood pressure (DBP) = 100 mm Hg. 9. Pregnant or lactating females. 10. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug. 11. Any other condition not specifically noted above which, in the judgment of the investigator, would preclude the patient from participating in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term safety and tolerability of ACE-536 in patients with low or intermediate-1 risk MDS who were previously enrolled in study A536-03.;Secondary Objective: Secondary:To evaluate - erythroid response defined as proportion of patients with: 1) A mean hemoglobin (Hgb) increase = 1.5 g/dL over an 8-week period as compared to baseline, not influenced by red blood cell (RBC) transfusion, in non-transfusion dependent (NTD) patients and 2) A decrease of = 4 units or = 50% of units of RBCs transfused over a period of 8 weeks, relative to the 8 weeks immediately prior to Day 1, in transfusion dependent (TD) patients. -rates of erythroid, neutrophil and platelet responses -rate of RBC transfusion independence lasting = 8 weeks in TD patients -time to HI-E response and duration of HI-E response -mean change in RBC transfusion burden in TD patients and mean change in hemoglobin levels in NTD patients -pharmacokinetic (PK) profile of ACE-536 -other pharmacodynamic (PD) effects Exploratory:To examine -biomarkers related to the transforming growth factor beta (TGF-ß) superfamily -self-reported quality of life using FACT-An questionnaire;Primary end point(s): Safety and tolerability will be assessed by adverse events, changes from baseline for clinical laboratory values and vital signs over time.;Timepoint(s) of evaluation of this end point: End of Treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy will be evaluated by determining the proportion of patients who have a modified HI-E erythroid response rate based upon the IWG 2006 criteria defined as 1) A mean hemoglobin increase = 1.5 g/dL over an 8-week period as compared to baseline, not influenced by RBC transfusion in NTD patients or 2) A decrease of = 4 units or = 50% of units of RBCs over a period of 8 weeks, relative to the number of units of RBCs transfused in the 8 weeks immediately prior to Cycle 1 Day 1 in TD patients. Baseline hemoglobin will be the average of two or more measures (not influenced by RBC transfusion) performed during the screening period for study A536-03 (for patients without interruption) or study A536-05 (for patients with interruption). Baseline units of RBCs transfused will be the 8-week period prior to study A536-03 (for patients without interruption) or study A536-05 (for patients with interruption). The erythroid response will be summarized using both a point estimate and its exact 95% confidence interval based on binomial distribution. No direct comparison testing with concurrent or historical controls will be performed. Other secondary efficacy/pharmacodynamic endpoints include: -Time to HI-E response and duration of HI-E response as per the IWG 2006 criteria and modified IWG criteria. -Mean RBC transfusion burden - Rate of RBC transfusion-free period lasting = 8 weeks in TD patients. -Mean hemoglobin level change in NTD patients -Other PD endpoints including: o Biomarkers for iron overload / metabolism o Relationship of biomarkers to response o Rates of HI-E, HI-N and HI-P Exploratory endpoints will include: • Biomarkers related to the TGF-beta superfamily. • Patient-reported quality of life in the expansion cohort using tools including but not limited to the FACT-An questionnaire. ;Timepoint(s) of evaluation of this end point: End of Treatment | — |
Countries
Germany
Contacts
Public ContactPeter G. Linde
Acceleron Pharma Inc.
Outcome results
None listed