A Safety and Efficacy Study to Evaluate Luspatercept in Subjects With Myeloproliferative Neoplasm-associated Myelofibrosis Who Have Anemia With and Without Red Blood Cell-transfusion Dependence

NCT03194542 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: ACE-536-MF-0012017-000322-35U1111-1197-1202
• Study Type: interventional
• Target: 95
• Locations: 4 countries
• Sites: 47

Brief Summary

This is a Phase 2, multicenter, open-label study to evaluate the efficacy and safety of luspatercept in subjects with MPN-associated myelofibrosis and anemia with and without RBC-transfusion dependence. The study is divided into a Screening Period, a Treatment Period (consisting of a Primary Phase, a Day 169 Disease Response Assessment, and an Extension Phase), followed by a Posttreatment Follow-up Period.

Conditions

Primary Myelofibrosis; Anemia

Keywords

Luspatercept; ACE-536; Myeloproliferative Neoplasm-Associated Myelofibrosis; Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia; Anemia; Red Blood Cell (RBC) Transfusion; Ruxolitinib

Outcome Measures

Primary Outcomes (1)

• The Number of Participants With Anemia Responses Over Any 84-Day Period During the Primary Treatment Period

  The number of participants that achieved anemia response as it relates to hemoglobin (Hgb) increase and red blood cell (RBC)-transfusion independence is defined below: Cohorts 1 (anemia only) and 3A: The number of participants achieving ≥ 1.5 g/dL hemoglobin increase from baseline over any consecutive 84-day period without an RBC transfusion from Day 1 up through and including Day 168. Cohorts 2 (RBC-transfusion dependent) and 3B: The number of participants who become RBC-transfusion free over any consecutive 84-day period from Day 1 up through and including Day 168. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose.

  Any consecutive "rolling" 84-day period from Day 1 through and including Day 168

Secondary Outcomes (20)

• Time to Anemia Response During the Primary Treatment Period

  From first dose up to first onset of anemia response (calculated from Day 1 through and including Day 168)

• Duration of Anemia Response

  From first dose through last day of longest response (calculated from Day 1 through end of treatment, up to approximately 232 weeks)

• The Number of RBC Units Transfused Per Participant Per 28 Days (Cohorts 2 and 3B Only)

  From Day 1 through end of treatment (up to approximately 232 weeks).

• The Number Participants Achieving >=50% RBC Transfusion Burden Reduction From Baseline Over Any 84-Day Period (Cohorts 2 and 3B Only)

  Baseline and from Day 1 through end of treatment (up to approximately 232 weeks).

• The Number of Participants Who Achieve ≥ 50% Reduction in Fatigue Symptom as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

  Baseline and from Day 1 through end of treatment (up to approximately 232 weeks)

Study Arms (1)

Luspatercept in subjects with MPN-associated myelofibrosis

EXPERIMENTAL

Subjects across each of the cohorts (Cohort 1, Cohort 2, Cohort 3A, and Cohort 3B) will receive luspatercept.

Drug: Luspatercept

Interventions

Luspatercept DRUG

Luspatercept is a recombinant fusion protein consisting of a modified form of the extracellular domain of the human active in receptor type IIB linked to the IgG1 Fc domain. Luspatercept, through a mechanism of action different from erythropoietin, works to correct ineffective erythropoiesis by promoting late-stage maturation of erythroblasts.

Also known as: ACE-536

Luspatercept in subjects with MPN-associated myelofibrosis

Eligibility Criteria

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

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study (with the enrollment date defined as the date in which the subject is assigned a cohort in Integrated Response Technology \[IRT\]) and receive their first dose of luspatercept:
• Subject is ≥18 years of age at the time of signing the informed consent form (ICF).
• Subject has Myeloproliferative neoplasm (MPN)-associated myelofibrosis (PMF, post- Post-polycythemia vera myelofibrosis (PV MF), and/or Post-essential thrombocythemia myelofibrosis (post-ET MF)) as confirmed from the most recent local bone marrow biopsy report according to the World Health Organization 2016 criteria.
• Subject has anemia defined as:
• Cohorts 1 and 3A
• Obtain ≥ 3 Hemoglobin (Hgb) levels of ≤ 9.5 g/dL recorded on ≥ 3 different days, including the day of dosing, in the 84-day period immediately up to the C1D1 date. There must be ≥ 14 days in between each Hgb measurement. No subjects with an interval ≥ 42 days between hemoglobin measurements will be enrolled.
• There must not be any Red blood cell (RBC) transfusions within the 84-day period immediately up to the C1D1 date.
• Cohorts 2 and 3B
• Average RBC-transfusion frequency: 4 to 12 RBC units/84 days immediately up to the C1D1 date. There must be no interval \> 56 days without ≥ 1 RBC-transfusion.
• Subjects must have a Hgb value of \< 13 g/dL on C1D1 prior to luspatercept administration.
• Only RBC transfusions given when the Hgb ≤ 9.5 g/dL are scored in determining eligibility.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
• Subject is not anticipated during the 6 months from the C1D1 date to receive a hematopoietic cell transplant.
• A female of childbearing potential (FCBP) for this study is defined as a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). FCBP participating in the study must:
• Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence\* from heterosexual contact.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment (with the enrollment date defined as the date in which the subject is assigned a cohort in Integrated Response Technology (IRT)):
• Subject use of hydroxyurea or other drugs with potential effects on hematopoiesis or ongoing adverse events from previous treatment ≤ 112 days immediately up to the enrollment date.
• a. Systemic corticosteroids are permitted for nonhematological conditions providing the subject is receiving a stable or decreasing dose for ≥ 84 days immediately up to enrollment and is receiving a constant dose equivalent to ≤ 10 mg prednisone for the 28 days immediately up to enrollment.
• Cohort 1 and 2 only: subjects treated with Janus kinase 2 gene (JAK2) inhibitors ≤ 112 days immediately up to the enrollment date or if anticipated/substantial likelihood for subject to receive ruxolitinib within the first 168 days on the study.
• Cohort 3 only: subjects not receiving ruxolitinib:
• for at least 280 days (40 weeks) without interruptions exceeding 2 consecutive weeks
• on a stable daily dose for at least 112 days (16 weeks) immediately up to the enrollment date as part of their standard-of-care therapy.
• Subject use of ESAs or androgenic steroids ≤ 112 days immediately up to the enrollment date.
• Initiation of iron chelation therapy (ICT) or change with ICT dose within ≤ 112 days up to the enrollment date.
• Subject with anemia from iron deficiency, B12 and folate deficiencies, hemolytic anemia, infection, or bleeding.
• Pregnant or breastfeeding females.
• Subject with blood myeloblasts ≥ 5%.
• Subject with major surgery within 8 weeks up to the enrollment date. Subject must have completely recovered from any previous surgery immediately up to the enrollment date.
• Subject with prior history of malignancies, other than disease under study, unless the subject has been free of the disease for ≥ 5 years. However, subject with the following history/concurrent conditions is allowed:
• Basal or squamous cell carcinoma of the skin

Sponsors & Collaborators

• Celgene: lead

Study Sites (47)

Local Institution - 102

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic - Arizona

Phoenix, Arizona, 85054, United States

Location

Local Institution - 103

Stanford, California, 94305, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Local Institution - 101

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Local Institution - 107

Orange City, Florida, 32763, United States

Location

Mid Florida Hematology and Oncology Centers, PA

Orange City, Florida, 32763, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Local Institution - 108

Tampa, Florida, 33612, United States

Location

Local Institution - 104

New York, New York, 10029, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Local Institution - 109

Cleveland, Ohio, 44195, United States

Location

Avera Research Institute

Sioux Falls, South Dakota, 57105, United States

Location

Local Institution - 105

Sioux Falls, South Dakota, 57105, United States

Location

Local Institution - 100

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center The University of Texas

Houston, Texas, 77030, United States

Location

Local Institution - 106

San Antonio, Texas, 78229, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

CHRU de Brest - Hopital Morvan

Brest, 29609, France

Location

Local Institution - 203

Brest, 29609, France

Location

Centre Hospitalier de Lens

Lens, 62307, France

Location

Local Institution - 201

Lens, 62307, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Local Institution - 200

Paris, 75010, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Local Institution - 202

Villejuif, 94805, France

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Local Institution - 304

Bergamo, 24127, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Local Institution - 300

Florence, 50134, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Local Institution - 301

Pavia, 27100, Italy

Location

Istituto Clinico Humanitas

Rozzano (MI), 20089, Italy

Location

Local Institution - 303

Rozzano (MI), 20089, Italy

Location

Local Institution - 302

Varese, 21100, Italy

Location

Ospedale di Circolo di Varese

Varese, 21100, Italy

Location

Belfast Health and Social Care Trust

Belfast Northern Ireland, BT9 7AB, United Kingdom

Location

Local Institution - 404

Cardiff, CF14 4XW, United Kingdom

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Local Institution - 400

Headington, Oxford, OX3 7LE, United Kingdom

Location

University of Oxford

Headington, Oxford, OX3 7LE, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Local Institution - 403

London, SE1 9RT, United Kingdom

Location

Imperial College London

London, W12 0HS, United Kingdom

Location

Local Institution - 402

London, W12 0HS, United Kingdom

Location

Related Publications (1)

• Gerds AT, Harrison C, Kiladjian JJ, Mesa R, Vannucchi AM, Komrokji R, Bose P, Kremyanskaya M, Mead AJ, Gotlib J, Rose S, Sanabria F, Marsousi N, Giuseppi AC, Jiang H, Palmer JM, McCaul K, Ribrag V, Passamonti F. Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis. Blood Adv. 2024 Sep 10;8(17):4511-4522. doi: 10.1182/bloodadvances.2024012939.

  PMID: 38820422 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Primary Myelofibrosis; Anemia

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2017
• First Posted: June 21, 2017
• Study Start: November 15, 2017
• Primary Completion: July 18, 2022
• Study Completion: July 18, 2022
• Last Updated: August 24, 2023
• Results First Posted: August 24, 2023

Record last verified: 2023-08

Locations

GB (9); FR (8); IT (10); US (20)