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Clinical Trial 19379

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT03194542

Phase: Phase II
Principal Investigator: Komrokji, Rami

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Overview

Study Title

A Phase 2, Multicenter, Open-Label Study To Evaluate The Efficacy And Safety Of Luspatercept (Ace-536) In Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis And Anemia With And Without Red Blood Cell-Transfusion Dependence

Summary

The main purpose of this study is to see if people with Myeloproliferative Neoplasm (MPN) Associated myelofibrosis that may or may not need blood transfusions will experience an increase of their hemoglobin or stop needing blood transfusions by taking luspatercept. The safety of luspatercept will be also evaluated in this study.

Objective

Primary Objective: The primary objective of the study is to evaluate the efficacy and safety of luspatercept for the treatment of anemia in subjects with myeloproliferative neoplasm (MPN)-associated myelofibrosis with and without red blood cell (RBC)-transfusion dependence. Secondary Objectives: To evaluate the safety of luspatercept in MPN-associated myelofibrosis. To evaluate the effect of luspatercept in MPN-associated myelofibrosis: - on the time to and duration of anemia response - on frequency of RBC transfusions and transfusion dependence - on symptom response improvement via the Myelofibrosis Symptom Assessment Form (MF-SAF) v4 - on health-related quality of life (HRQoL) via the EQ-5D-5L and Functional Assessment of Cancer Therapy - Anemia (FACT-An) questionnaires. To evaluate population pharmacokinetics of luspatercept in subjects with MPNassociated myelofibrosis with and without RBC-transfusion dependence. Explanatory Objectives: To explore the relationship between luspatercept exposure and measures of efficacy and toxicity. To explore biomarkers related to efficacy parameters and markers related to mechanism of action of luspatercept. - Activin receptor IIB ligands such as growth differentiation factor 11 (GDF11) and, - Activin B, - Inflammatory cytokines such as interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-a), - Serum markers related to fibrogenesis such as transforming growth factor-beta 1 (TGF-b1) and thrombopoietin (TPO), - Circulating blasts (CD34+ cells), - Gene expression profiling or other similar evaluation related to drug mechanism of action. To explore MPN-associated myelofibrosis-related mutations relative to disease progression and/or drug response.

Treatments

Therapies

Therapy (NOS)

Medications

ACE-536 (Luspatercept); Luspatercept ()

Inclusion Criteria

18 years of age or older at the time of signing the informed consent form (ICF).

Have 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 World Health Organization 2016 criteria (Arber, 2016).

Has anemia as defined in protocol documentation for each cohort.

Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.

Not anticipated during the 6 months from the C1D1 date to receive a hematopoietic cell transplant.

Willing to adhere to study birth control and pregnancy test requirements.

Must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.

Willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria

The 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. 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 less than or equal to 10 mg prednisone for the 28 days immediately up to enrollment.

Cohort 1 and 2 only: have been treated with Janus kinase 2 gene (JAK2) inhibitors less than or equal to 112 days immediately up to the enrollment date or if anticipated/substantial likelihood for participant to receive ruxolitinib within the first 168 days on the study.

Cohort 3 only: not receiving ruxolitinib

The use of ESAs or androgenic steroids less than or equal to 112 days immediately up to the enrollment date.

Starting iron chelation therapy (ICT) or changing ICT dose within less than or equal to 112 days up to the enrollment date.

Anemia from iron deficiency, B12 and folate deficiencies, hemolytic anemia, infection, or bleeding.

Pregnant or breastfeeding females.

Major surgery within 8 weeks up to the enrollment date. Must have completely recovered from any previous surgery immediately up to the enrollment date.

Prior history of malignancies, other than disease under study, unless has been free of the disease for ≥ 5 years. However, 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).

Prior therapy of luspatercept or sotatercept.

Prior hematopoietic cell transplant.

Any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (e.g., imprisoned or institutionalized) that would prevent the patient from participating in the study.

Any condition including the presence of laboratory abnormalities at screening, which places the patient at unacceptable risk if he/she were to participate in the study.

Additional criteria may apply.

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