Study of Luspatercept for the Treatment of Anemia in Patients With Myelodysplastic Syndrome (MDS) (MK-6143-001)

NCT01749514 | Completed Phase 2 Results

• 3 other identifiers: A536-03MK-6143-0012012-002523-14
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effects of luspatercept (MK-6143, formerly called ACE-536) on anemia in patients with low or intermediate-1 risk myelodysplastic syndrome (MDS). There is no primary hypothesis in this study.

Conditions

Anemia

Keywords

Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Percentage of Low Transfusion Burden (LTB) Participants With Modified Erythroid Response (mHI-E)

  The mHI-E for LTB participants was defined as a hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 days or rolling 2 weeks (in the absence of red blood cell \[RBC\] transfusions). Hemoglobin measurements within 7 days following RBC transfusion were excluded from analysis. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. Rolling 2 weeks was defined as any consecutive 2 weeks during the study. The percentage of LTB participants with mHI-E were reported.

  Any consecutive 2 weeks during the study (up to approximately 75 weeks)

• Percentage of High Transfusion Burden (HTB) Participants With mHI-E

  The mHI-E for HTB participants was defined as a ≥4 units or ≥50% reduction in RBC transfusion burden during any rolling 8-week window compared to baseline. HTB participants were those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. The percentage of HTB participants with mHI-E were reported.

  Any consecutive 8 weeks during the study (up to approximately 75 weeks)

Secondary Outcomes (28)

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 24 weeks

• Number of Participants Who Discontinued Study Treatment Due To an AE

  Up to approximately 12 weeks

• Rate of Erythroid Response (HI-E) Per International Working Group (IWG) 2006 Response Criteria

  Any consecutive 8 Weeks during the study treatment (up to approximately 75 weeks)

• Rate of Platelet Response (HI-P) Per IWG 2006 Criteria

  Any consecutive 8 Weeks during the study treatment (up to approximately 75 weeks)

• Rate of Neutrophil Response (HI-N) Per IWG 2006 Criteria

  Any consecutive 8 Weeks during the study treatment (up to approximately 75 weeks)

Study Arms (8)

Luspatercept 0.125mg/kg (Cohort 1)

EXPERIMENTAL

Participants receive luspatercept 0.125mg/kg as a subcutaneous (SC) injection every 3 weeks (Q3W) on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).

Drug: Luspatercept

Luspatercept 0.25mg/kg (Cohort 2)

EXPERIMENTAL

Participants receive luspatercept titrated up to 0.25mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).

Drug: Luspatercept

Luspatercept 0.50mg/kg (Cohort 3)

EXPERIMENTAL

Participants receive luspatercept titrated up to 0.50mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).

Drug: Luspatercept

Luspatercept 0.75mg/kg (Cohort 4)

EXPERIMENTAL

Participants receive luspatercept titrated up to 0.75mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).

Drug: Luspatercept

Luspatercept 1.00mg/kg (Cohort 5)

EXPERIMENTAL

Participants receive luspatercept titrated up to 1.00mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).

Drug: Luspatercept

Luspatercept 1.33mg/kg (Cohort 6)

EXPERIMENTAL

Participants receive luspatercept titrated up to 1.33mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).

Drug: Luspatercept

Luspatercept 1.75mg/kg (Cohort 7)

EXPERIMENTAL

Participants receive luspatercept titrated up to 1.75mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).

Drug: Luspatercept

Expansion Cohort

EXPERIMENTAL

Participants receive an initial dose of luspatercept 1.0mg/kg SC on Day 1 of the Cycle 1 (Cycle length = 21 days). For each subsequent cycle (up to 5 cycles), the dose was titrated via Fibonacci scheme up to a maximum dose of 1.75mg/kg based on the safety review team (SRT) recommendations

Drug: Luspatercept

Interventions

Luspatercept DRUG

Participants receive luspatercept up to 1.75mg/kg subcutaneously (SC) every 3 weeks for up to 5 cycles (each cycle length = 21 days).

Also known as: MK-6143, A536

Expansion Cohort; Luspatercept 0.125mg/kg (Cohort 1); Luspatercept 0.25mg/kg (Cohort 2); Luspatercept 0.50mg/kg (Cohort 3); Luspatercept 0.75mg/kg (Cohort 4); Luspatercept 1.00mg/kg (Cohort 5); Luspatercept 1.33mg/kg (Cohort 6); Luspatercept 1.75mg/kg (Cohort 7)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented diagnosis of idiopathic/de novo myelodysplastic syndrome (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML), according to WHO criteria (white blood count, 13,000/uL), 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
• Anemia defined as:
• 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 red blood cell (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 Transfusion dependent, defined as having received ≥4 units of RBCs within 8 weeks prior to Cycle 1 Day 1
• Serum erythropoietin levels and prior erythropoiesis-stimulating agent (ESA) treatment:
• Dose escalation cohorts and expansion cohort 1 patients: Serum erythropoietin level \>500 U/L, OR, if ≤500 U/L, patient is non-responsive, refractory, or intolerant to erythropoiesis-stimulating agents (ESAs), or ESAs are contraindicated or unavailable
• Expansion cohort 2 patients: If patient is RS+ (defined as having ≥15% ring sideroblasts in the bone marrow), no prior ESA treatment and serum erythropoietin level ≤ 200 U/L. If a patient is RS- (defined as having \<15% ring sideroblasts in the bone marrow), prior ESA treatment and any serum erythropoietin level is allowed
• No alternative treatment options, per applicable MDS guidelines, are available and/or appropriate for the patient, at the discretion of the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia).
• Adequate renal (creatinine ≤2 x upper limit of normal \[ULN\]) and hepatic (total bilirubin \<2 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3 x ULN) function
• 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)
• 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 luspatercept. 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 luspatercept, 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 luspatercept
• Patients are able to adhere to the study visit schedule, understand and comply with all protocol requirements
• Patients understand and are able to provide written informed consent

You may not qualify if:

• Prior treatment with azacitidine or decitabine
• Treatment within 28 days prior to Cycle 1 Day 1 with:
• Erythropoiesis stimulating agent (ESA)
• Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF)
• Lenalidomide
• Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1
• 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
• 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
• Platelet count \<30 x 109/L.
• 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
• History of stroke, deep venous thrombosis (DVT) or arterial embolism within 6 months prior to Cycle 1 Day 1
• Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV)
• 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
• Uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 150 mm Hg or diastolic BP ≥ 100 mm Hg
• Pregnant or lactating females

Sponsors & Collaborators

• Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA: lead

Study Sites (1)

Acceleron Investigative Site

Dresden, Germany

Location

Related Publications (2)

• Platzbecker U, Gotze KS, Kiewe P, Germing U, Mayer K, Radsak M, Wolff T, Chromik J, Sockel K, Oelschlagel U, Haase D, Illmer T, Al-Ali HK, Silling G, Reynolds JG, Zhang X, Attie KM, Shetty JK, Giagounidis A. Long-Term Efficacy and Safety of Luspatercept for Anemia Treatment in Patients With Lower-Risk Myelodysplastic Syndromes: The Phase II PACE-MDS Study. J Clin Oncol. 2022 Nov 20;40(33):3800-3807. doi: 10.1200/JCO.21.02476. Epub 2022 Aug 23.

  PMID: 35998303 DERIVED

• Platzbecker U, Germing U, Gotze KS, Kiewe P, Mayer K, Chromik J, Radsak M, Wolff T, Zhang X, Laadem A, Sherman ML, Attie KM, Giagounidis A. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017 Oct;18(10):1338-1347. doi: 10.1016/S1470-2045(17)30615-0. Epub 2017 Sep 1.

  PMID: 28870615 DERIVED

MeSH Terms

Conditions

Anemia; Myelodysplastic Syndromes

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2012
• First Posted: December 13, 2012
• Study Start: January 21, 2013
• Primary Completion: October 22, 2018
• Study Completion: October 22, 2018
• Last Updated: July 29, 2024
• Results First Posted: July 29, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)