Study of ACE-536 for the Treatment of Anemia in Patients With Myelodysplastic Syndromes (MDS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Acceleron Pharma, Inc.
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01749514
First received: December 10, 2012
Last updated: October 10, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the effects of ACE-536 on anemia in patients with low or intermediate-1 risk MDS.


Condition Intervention Phase
Anemia
Drug: ACE-536
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open Label, Ascending Dose Study of ACE-536 for the Treatment of Anemia in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS)

Resource links provided by NLM:


Further study details as provided by Acceleron Pharma, Inc.:

Primary Outcome Measures:
  • Proportion of patients who have a modified erythroid response (mHI-E). [ Time Frame: Assessed at approximately 28 weeks from patient screening. ] [ Designated as safety issue: No ]
    mHI-E defined as a hemoglobin increase of ≥ 1.5 g/dL from baseline for ≥ 14 days (in the absence of red blood cell [RBC] transfusions) in non-transfusion dependent patients, or, a reduction of either ≥ 4 units or ≥ 50% of units of RBCs transfused compared to pre treatment in transfusion dependent patients.


Secondary Outcome Measures:
  • Number of patients with adverse events. [ Time Frame: From treatment initiation to End-of-Study visit (approximately 28 weeks later). ] [ Designated as safety issue: Yes ]
  • Rates of erythroid, neutrophil and platelet (HI-E, HI-N and HI-P) responses. [ Time Frame: Measured during any 8 week period on study, up tp 28 weeks from patient screening, compared with the 8-week period prior to study day 1. ] [ Designated as safety issue: No ]
  • Time to mHI-E response. [ Time Frame: Measured over the course of study, up to approximately 24 weeks from initiation of dosing on study day 1. ] [ Designated as safety issue: No ]
  • Frequency of RBC transfusions in transfusion-dependent patients. [ Time Frame: Approximately 28 weeks from patient screening. ] [ Designated as safety issue: No ]
  • ACE-536 pharmacokinetics (e.g., serum half-life, peak serum concentration, time to peak concentration, etc.). [ Time Frame: Measured at multiple time points over the course of treatment, from study day 1 to approximately 24 weeks. ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: January 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACE-536
Subjects assigned to 1 of 7 possible dosing groups.
Drug: ACE-536
Subjects receive ACE-536 administered subcutaneously (SC) every 3 weeks for up to 5 cycles.
Other Name: luspatercept

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Documented diagnosis of idiopathic/de novo MDS or non-proliferative chronic myelomonocytic leukemia (CMML), according to WHO criteria, that meets International Prognostic Scoring System (IPSS) classification of low or intermediate-1 risk disease as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC) obtained during screening.
  2. Anemia defined as:

    1. Mean hemoglobin concentration < 10.0 g/dL of 2 measurements (one performed within one day prior to Cycle 1 Day 1 and the other performed 7-28 days prior to Cycle 1 Day 1, not influenced by RBC transfusion within 7 days of measurement) for non-transfusion dependent patients (defined as having received < 4 units of RBCs within 8 weeks prior to Cycle 1 Day 1), OR
    2. Transfusion dependent, defined as having received ≥ 4 units of RBCs within 8 weeks prior to Cycle 1 Day 1.

    of RBCs for hemoglobin ≤ 9.0 g/dL within 8 weeks prior to Cycle 1 Day 1.

  3. Serum erythropoietin level > 500 U/L, OR, if ≤ 500 U/L, patient is non-responsive to, refractory to, or intolerant of erythropoiesis-stimulating agents (ESAs), or ESAs are contraindicated or unavailable.
  4. No alternative treatment options, per applicable MDS guidelines, are available and/or appropriate for the patient, at the discretion of the investigator.
  5. ECOG performance status of 0, 1, or 2 (if related to anemia).
  6. Adequate renal (creatinine ≤ 2 x upper limit of normal [ULN]) and hepatic (total bilirubin < 2 x ULN and AST and ALT < 3 x ULN) function.
  7. Adequate transferrin saturation (≥ 15%), ferritin (≥ 50 µg/L), folate (≥ 4.5 nmol/L [≥ 2.0 µg/L]) and vitamin B12 (≥ 148 pmol/L [≥ 200 pg/mL]) during screening (supplementation and retest during screening is acceptable).
  8. 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. 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 the first dose of ACE-536.
  9. Patients are able to adhere to the study visit schedule, understand and comply with all protocol requirements.
  10. Patients understand and are able to provide written informed consent.

Key Exclusion Criteria:

  1. Prior treatment with azacitidine or decitabine.
  2. Treatment within 28 days prior to Cycle 1 Day 1 with:

    i) Erythropoiesis stimulating agent (ESA), ii) Granulocyte colony-stimulating factor (G-CSF) and granulocyte- macrophage colony stimulating factor (GM-CSF), iii) Lenalidomide.

  3. Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1.
  4. Treatment with another investigational drug or device, or approved therapy for investigational use ≤ 28 days prior to Cycle 1 Day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer.
  5. 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.
  6. Platelet count < 30 x 109/L.
  7. Any active infection requiring parenteral antibiotic therapy within 28 days prior to Cycle 1 Day 1 or oral antibiotics within 14 days of Cycle 1 Day 1.
  8. History of stroke, deep venous thrombosis (DVT) or arterial embolism within 6 months prior to Cycle 1 Day 1.
  9. Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV).
  10. Any malignancy other than MDS which has not been in remission and/or has required systemic therapy including radiation, chemotherapy, hormonal therapy or surgery, within the last year prior to Cycle 1 Day 1.
  11. Uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 150 mm Hg or diastolic BP ≥ 100 mm Hg.
  12. Pregnant or lactating females.
  13. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug.
  14. Any other condition not specifically noted above which, in the judgment of the investigator, would preclude the patient from participating in the study.
  15. Transfusion event within 7 days prior to Cycle 1 Day 1.
  16. Prior treatment with sotatercept (ACE-011) or ACE-536.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01749514

Contacts
Contact: Clinical Trials Manager clinicaltrials536@acceleronpharma.com

Locations
Germany
Acceleron Investigative Site Recruiting
Dresden, Germany
Sponsors and Collaborators
Acceleron Pharma, Inc.
  More Information

No publications provided

Responsible Party: Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01749514     History of Changes
Other Study ID Numbers: A536-03
Study First Received: December 10, 2012
Last Updated: October 10, 2014
Health Authority: Germany: Paul-Ehrlich-Institut
United States: Food and Drug Administration

Keywords provided by Acceleron Pharma, Inc.:
Myelodysplastic Syndrome

Additional relevant MeSH terms:
Anemia
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Pathologic Processes
Precancerous Conditions

ClinicalTrials.gov processed this record on October 29, 2014