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NCT03682536

Efficacy and Safety Study of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS) in ESA Naïve Subjects Who Require Red Blood Cell Transfusions

Datenbasis: WHO (Import vom 26.01.2020)
Geändert: 12.01.2020
Krankheitskategorie:

Health conditions (Datenquelle: WHO)

Myelodysplastic Syndromes

Interventions (Datenquelle: WHO)

Drug: Luspatercept;Drug: Epoetin alfa

Inclusion/Exclusion Criteria (Datenquelle: WHO)


Inclusion Criteria:

Subjects must satisfy the following criteria to be randomized in the study:

1. Subject is = 18 years of age the time of signing the informed consent form (ICF).

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

3. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.

4. Subject has a documented diagnosis of MDS according to WHO 2016 classification that
meets IPSS-R classification of very low, low, or intermediate risk disease, and:

• < 5% blasts in bone marrow.

5. Subject has an endogenous serum erythropoietin (sEPO) level of < 500 U/L.

6. Subject requires RBC transfusions, as documented by the following criteria:

• Average transfusion requirement of 2 - 6 units/8 weeks of pRBCs confirmed for a
minimum of 8 weeks immediately preceding randomization.

- Hemoglobin levels at the time of or within 7 days prior to administration of a
RBC transfusion must have been = 9.0 g/dL with symptoms of anemia (or = 7 g/dL in
the absence of symptoms) in order for the transfusion to be counted towards
meeting eligibility criteria. Red blood cell transfusions administered when Hgb
levels were > 9.0 g/dL (or > 7 g/dL in the absence of symptoms) and/or RBC
transfusions administered for elective surgery, infections or bleeding events
will not qualify as a required transfusion for the purpose of meeting eligibility
criteria or stratification.

- The hemoglobin level after the last RBC transfusion prior to randomization must
be < 11.0 g/dL (centrally or locally analyzed).

7. Subject has Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.

8. Females of childbearing potential (FCBP), defined as a sexually mature woman who:

1) has not undergone a hysterectomy or bilateral oophorectomy or 2) 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), must:

- Have two negative pregnancy tests as verified by the investigator prior to starting
study therapy (unless the screening pregnancy test was done within 72 hours of W1D1).
She must agree to ongoing pregnancy testing during the course of the study, and after
end of study treatment.

- If sexually active, agree to use, and be able to comply with, highly effective
contraception without interruption, 5 weeks prior to starting investigational product,
during the study therapy (including dose interruptions), and for 12 weeks after
discontinuation of study therapy. 9. Male subjects must:

- Practice true abstinence (which must be reviewed prior to each IP administration or on
a monthly basis [eg, in the event of dose delays]) or agree to use a condom (latex or
non-latex, but not made out of natural [animal] membrane) 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 following investigational
product discontinuation, even if he has undergone a successful vasectomy.

Exclusion Criteria:

The presence of any of the following will exclude a subject from randomization (with the
randomization date defined as the date in which the subject is randomized in IRT):

1. Subject with the any of the following prior treatments:

- Erythropoiesis-stimulating agents (ESAs)

- Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage
colony-stimulating factor (GM-CSF), unless given for treatment of febrile
neutropenia

- Disease modifying agents (eg, immune-modulatory drug [IMiDs such as lenalidomide]

- Except if the subject received = 1 week of treatment with a disease
modifying agent = 8 weeks from randomization, at the investigator's
discretion.

- Hypomethylating agents

- Subjects may be randomized at the investigator's discretion contingent that
the subject received no more than 2 doses of HMA. The last dose must be = 8
weeks from the date of randomization.

- Luspatercept (ACE-536) or sotatercept (ACE-011)

- Immunosuppressive therapy for MDS

- Hematopoietic cell transplant

2. Subject with MDS associated with del(5q) cytogenetic abnormality or MDS unclassifiable
(MDS-U) according to WHO 2016 classification.

3. Subject with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) according to WHO
2016 classification (ie, Chronic myelomonocytic leukemia (CMML), Atypical chronic
myeloid leukemia (aCML), BCR-ABL12, Juvenile myelomonocytic leukemia (JMML), MDS/MPN
with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), MDS/MPN unclassifiable.

4. Subject with secondary MDS, ie, MDS that is known to have arisen as the result of
chemical injury or treatment with chemotherapy and/or radiation for other diseases.

5. Subject with known clinically significant anemia due to iron, vitamin B12, or folate
deficiencies, or autoimmune or hereditary hemolytic anemia, or hypothyroidism, or any
type of known clinically significant bleeding or sequestration. Subject with drug
induced anemia (eg, mycophenolate).

• Iron deficiency to be determined by serum ferritin < 100 µg/L and additional testing
if clinically indicated (eg, calculated transferrin saturation [iron/total iron
binding capacity = 20%] or bone marrow aspirate stain for iron).

6. Subject with known history of diagnosis of AML.

7. Subject receiving any of the following treatment within 8 weeks prior to
randomization:

- Anticancer cytotoxic chemotherapeutic agent or treatment

- Systemic corticosteroid, except for subjects on a stable or decreasing dose for =
1 week prior to randomization for medical conditions other than MDS

- Iron-chelating agents, except for subjects on a stable or decreasing dose for at
least 8 weeks prior to randomization

- Other RBC hematopoietic growth factors (eg, Interleukin-3)

- Androgens, unless to treat hypogonadism

- Hydroxyurea

- Oral retinoids (except for topical retinoids)

- Arsenic trioxide

- Interferon and interleukins

- Investigational drug or device, or approved therapy for investigational use

Weitere Angaben zur Studie im WHO-Primärregister

https://clinicaltrials.gov/show/NCT03682536

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03682536

Weitere Informationen zur Studie

Registrationsdatum der Studie

07.09.2018

Einschluss der ersten teilnehmenden Person

02.01.2019

Rekrutierungsstatus

Recruiting

Wissenschaftlicher Titel (Datenquelle: WHO)

A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alpha for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Due to Myelodysplastic Syndrome (MDS) ESA in Native Subjects Who Require Red Blood Cell Transfusions

Studientyp (Datenquelle: WHO)

Interventional

Design der Studie (Datenquelle: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Datenquelle: WHO)

Phase 3

Primäre Endpunkte (Datenquelle: WHO)

Red Blood Cell Transfusion Independence (RBCTI) for 24 weeks

Sekundäre Endpunkte (Datenquelle: WHO)

Overall survival;Time to AML;Progression to AML;Antidrug antibodies (ADA);Pharmacokinetic - Cmax;Pharmacokinetic - AUC;Adverse Event (AE);The Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An) questionnaire;The European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30);RBC-TI for a consecutive 24-week period;RBC-TI during Weeks 4-24;For subjects with RBC transfusion burden of =4 units/8 weeks at baseline:;RBC transfusion burden on treatment;Time to first Red blood cell (RBC) transfusion;Time to RBC-TI = 84 days;Duration of RBC-TI = 84 days;RBC-TI for = 84 days;Duration of Red blood cell transfusion independence (RBC-TI) = 24 weeks;Duration of HI-E;Time to Hematologic improvement - erythroid response (HI-E);Mean hemoglobin increase = 1.5 g/dL;Hematologic improvement - erythroid response (HI-E) per International Working Group (IWG) within 24 weeks

Kontakt für Auskünfte (Datenquelle: WHO)

Please refer to primary and secondary sponsors

Studiendurchführungsorte

Durchführungsländer (Datenquelle: WHO)

Australia, Austria, Belgium, Canada, Czechia, France, Germany, Italy, Japan, Lithuania, Netherlands, Poland, Portugal, Russian Federation, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States

Kontakt für weitere Auskünfte zur Studie

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

Rodrigo Ito, MD;Associate Director Clinical Trial Disclosure
Celgene
1-888-260-1599
clinicaltrialdisclosure@celgene.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Rodrigo Ito, MD;Associate Director Clinical Trial Disclosure
Celgene
1-888-260-1599
clinicaltrialdisclosure@celgene.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

Celgene

Weitere Sponsoren (Datenquelle : WHO)

Acceleron Pharma, Inc.

Weitere Studienidentifikationsnummern

Secondary ID (Datenquelle: WHO)

U1111-1218-1810;2017-003190-34;ACE-536-MDS-002