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

Completed · Phase 2

Conditions studied: Primary Myelofibrosis, Anemia

In brief

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.

Key facts

Study ID

NCT03194542

Run by

Celgene

People needed

95

Starts

2017-11-15

Expected to finish

2022-07-18

Last updated by the study team

2023-08-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
• Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception** without interruption, 28 days prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks (approximately 5 times the mean terminal halflife of luspatercept based on multiple-dose pharmacokinetics [PK] data) after discontinuation of study therapy.
• Male subjects must:
• a. Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5 times the mean terminal half-life of luspatercept based on multiple-dose PK data) following investigational product discontinuation, even if he has undergone a successful vasectomy
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

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
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
• Subject with prior therapy of luspatercept or sotatercept.
• Subject participation in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices within 30 days immediately up to the enrollment date.
• Subject with prior hematopoietic cell transplant.
• Subject with any of the following laboratory abnormalities:
• Neutrophils < 1 x 109/L
• White blood count (WBC) > 100 x 109/L
• Platelets

Where it is running

• Local Institution - 102 — Phoenix, Arizona, United States
• Mayo Clinic - Arizona — Phoenix, Arizona, United States
• Local Institution - 103 — Stanford, California, United States
• Stanford Cancer Center — Stanford, California, United States
• Local Institution - 101 — Jacksonville, Florida, United States
• Mayo Clinic - Jacksonville — Jacksonville, Florida, United States
• Local Institution - 107 — Orange City, Florida, United States
• Mid Florida Hematology and Oncology Centers, PA — Orange City, Florida, United States
• H. Lee Moffitt Cancer Center and Research Institute — Tampa, Florida, United States
• Local Institution - 108 — Tampa, Florida, United States
• Local Institution - 104 — New York, New York, United States
• Mount Sinai Medical Center — New York, New York, United States
• Cleveland Clinic — Cleveland, Ohio, United States
• Local Institution - 109 — Cleveland, Ohio, United States
• Avera Research Institute — Sioux Falls, South Dakota, United States
• Local Institution - 105 — Sioux Falls, South Dakota, United States
• Local Institution - 100 — Houston, Texas, United States
• MD Anderson Cancer Center The University of Texas — Houston, Texas, United States
• Local Institution - 106 — San Antonio, Texas, United States
• University of Texas Health Science Center at San Antonio — San Antonio, Texas, United States
• CHRU de Brest - Hopital Morvan — Brest, France
• Local Institution - 203 — Brest, France
• Centre Hospitalier de Lens — Lens, France
• Local Institution - 201 — Lens, France
• Hopital Saint Louis — Paris, France

Full record on ClinicalTrials.gov

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