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A Study to Evaluate Long-term Safety in Subjects Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials

  • Clinicaltrials.gov identifier

    NCT04064060

  • Recruitment Status

    Recruiting

  • First Posted

    August 21, 2019

  • Last update posted

    December 1, 2020

Study Description

Brief summary:

A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept, to the following subjects: - Subjects receiving luspatercept on a parent protocol at the time of their transition to the rollover study, who tolerate the protocol-prescribed regimen in the parent trial and, in the opinion of the investigator, may derive clinical benefit in the opinion of the investigator from continuing treatment with luspatercept. - Placebo arm subjects from parent protocol (at the time of unblinding or in follow-up) crossing over to luspatercept treatment (provided subjects have met all requirements for entering the rollover study as per the parent protocol). - Subjects in the follow-up phase previously treated with luspatercept or placebo in the parent protocol will continue into long-term post-treatment follow-up in the rollover study until the follow-up commitments are met (unless they meet requirements as per parent protocol to cross-over to luspatercept treatment). The study design is divided into the Transition Phase, Treatment Phase and Follow-up Phase. Subjects will enter transition phase and depending on their background will enter either the treatment phase or the Long-term Post-treatment Follow-up (LTPTFU) phase. - Transition Phase (Screening): up to 21 days prior to enrollment - Treatment Phase: For subjects in luspatercept treatment the dose and schedule of luspatercept in this study will be the same as the last dose and schedule in the parent luspatercept study. For placebo arm subjects from parent protocol (at the time of unblinding or in follow-up) crossing over to luspatercept treatment (provided subjects have met all requirements for entering the rollover study as per the parent protocol) will start at a luspatercept dose of 1.0 mg/kg every 3 weeks (Q3W). This does not apply to subjects that are in long-term follow-up from the parent protocol. - Follow-up Phase: - 42 Day Safety Follow-up Phase: subjects will be followed for 42 days after the last dose of luspatercept, for the assessment of safety-related parameters and adverse event (AE) reporting. - Long-term Post-treatment Follow-up (LTPTFU) Phase: All subjects who are continuing in the LTPTFU Phase, will continue to be followed for 5 years from Dose 1 of the parent protocol, or 3 years of post-treatment from last dose of the parent protocol, whichever occurs later. Subjects will be followed every 6 months until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. Subjects will also be monitored for progression to AML or any malignancies/pre- malignancies. New anticancer or disease related therapies should be collected at the same time schedule. Subjects transitioning from a parent luspatercept study in post-treatment follow-up (safety or LTPTFU) will continue from the same equivalent point in this rollover study. The rollover study will be terminated, and relevant subjects will discontinue from the study when all subjects fulfill 5 years from Dose 1 of the parent protocol, or 3 years of post-treatment from last dose of the parent protocol, whichever occurs later. The shift to commercial drug is an alternative way to stop the study.

  • Condition or Disease:Beta-thalassemia
    Myelodysplastic Syndromes (MDS)
    Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis
  • Intervention/Treatment: Drug: Luspatercept
  • Phase: Phase 3

Detailed Description

N/A

Study Design

  • Study Type: Interventional
  • Estimated Enrollment: 665 participants
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Phase 3b, Open Label, Single-arm Rollover Study to Evaluate Long Term Safety in Subjects Who Have Participated in Other Luspatercept (Ace-536) Clinical Trials.
  • Actual Study Start Date: August 2019
  • Estimated Primary Completion Date: March 2030
  • Estimated Study Completion Date: March 2030

Arms and interventions

Arm Intervention/treatment
Experimental: ACE-536
Luspatercept will be administered as a subcutaneous (SC) injection to subjects by the study staff at the clinical site and administration will be documented in the subject's source record.
Drug: Luspatercept
Luspatercept (ACE-536), an erythroid maturation agent, is a recombinant fusion protein consisting of a modified form of the extracellular domain (ECD) of the human activin receptor type IIB (ActRIIB) linked to the human immunoglobin G 1 (IgG1) Fc domain. ActRIIB receptor and its ligands are members of the transforming growth factor-β (TGF-β) superfamily. Members of the TGF-β superfamily ligands, through their binding to activin receptors, are involved in modulating the differentiation of late-stage erythrocyte precursors (normoblasts) in the bone marrow. Luspatercept for injection is formulated as a sterile, preservative-free, lyophilized cake/powder. Luspatercept for injection is available in 25 mg and 75 mg vials and when reconstituted with water for injection, each consists of 50 mg/mL luspatercept in a 10 mM citrate buffer-based solution

Outcome Measures

  • Primary Outcome Measures: 1. Adverse Events (AEs) [ Time Frame: From enrollment until at least 42 Day Safety Follow-up Phase or EOS (Approximately 5 years). ]
    Type, frequency, severity of AEs, relationship of treatment emergent adverse events to luspatercept
  • 2. Number of subjects progressing to high/very high risk MDS or AML. [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    Progression to high/very high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (MDS and myelofibrosis [MF] only).
  • 3. Percentage of subjects progressing to high/very high risk MDS or AML [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    Progression to high/very high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (MDS and myelofibrosis [MF] only)
  • 4. Number of subjects developing other malignancies/pre-malignancies [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    Development of other malignancies/pre-malignancies
  • 5. Percentage of subjects developing other malignancies/pre-malignancies [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    Development of other malignancies/pre-malignancies
  • Secondary Outcome Measures: 1. Overall Survival [ Time Frame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years) ]
    Time from date of randomization until death from any cause

Eligibility Criteria

  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Subjects must meet all the following criteria to be enrolled in this study:

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

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

3. Subject has been participating in a luspatercept trial and continues to fulfill all
the requirements of the parent protocol and the subject has been either:

1. Assigned to luspatercept treatment, continues to receive clinical benefit in the
opinion of the investigator and should continue to receive luspatercept
treatment, OR

2. Assigned to placebo arm in the parent protocol (at the time of unblinding or in
follow-up) and should cross over to luspatercept treatment, OR

3. Assigned to the Follow-up Phase of the parent protocol, previously treated with
luspatercept or placebo in the parent protocol who shall continue into Long-term
Post-treatment Follow-up Phase in the rollover study until the follow-up
commitments are met (unless requirements are met as per parent protocol to
crossover to luspatercept treatment).

4. Subject understands and voluntarily signs an informed consent document prior to any
study-related assessments or procedures being conducted.

5. Subject demonstrates compliance, as assessed by the investigator, with the parent
study protocol requirements.

6. Applies to on treatment subjects only- females of childbearing potential (FCBP)
defined as a sexually mature woman 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) and must:

1. Have two 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 therapy. This applies even if the subject practices true
abstinence* from heterosexual contact.

2. 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
highly effective, contraception without interruption, 35 days prior to starting
investigational product (IP), during the study therapy (including dose interruptions),
and for 84 days after discontinuation of study therapy.

7. Applies to on treatment subjects only- 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 84 days
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 enrollment:

1. Applies to on treatment subjects only- Concomitant use of any medications/procedures
that are prohibited in the parent luspatercept protocol.

2. Subject has met one or more criteria for study discontinuation as stipulated in the
parent luspatercept protocol.

3. First luspatercept transition visit into rollover study > 21 days after end of study
(EOS) visit (last dose/visit in case of no EOS visit) of the parent luspatercept study
with the exception of those subjects already in the Post-treatment Follow up Phase
from the parent study. Note-Subject with current dose delays from the parent protocol
during the Transition Phase, will continue in the rollover protocol regardless of the
delay.

4. Applies to on treatment subjects only- Pregnant or breastfeeding females.

5. Subject has any significant medical condition, laboratory abnormality, psychiatric
illness, or is considered vulnerable by local regulations (eg, imprisoned or
institutionalized) that would prevent the subject from participating in the study.

6. Subject has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study.

7. Subject has any condition that confounds the ability to interpret data from the study.

Contacts and Locations

Contacts

Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations

France
Hopital Henri Mondor
Creteil

France
CHU d'Angers
Angers

France
Centre Hospitalier Universitaire de Grenoble Hopital Albert Michallon
La Tronche

France
CHRU de Lille-Hopital Claude Huriez
Lille

France
Hopitaux de La Timone
Marseille Cedex 9

France
Hopital Saint Louis
Paris

France
Hopital Haut Leveque
Pessac Cedex

France
Centre Hospitalier Lyon Sud
Pierre Benite cedex

France
Hopital civil
Strasbourg

France
Institut Universitaire du Cancer de Toulouse - Oncopole
Toulouse Cedex 9

France
Hopital Bretonneau
Tours

United States, California
Childrens Hospital Los Angeles RHU
Los Angeles

United States, California
UCSF Benioff Children's Hospital Oakland
Oakland

United States, California
Stanford Cancer Center
Stanford

United States, Florida
Moffitt Cancer Center
Tampa

United States, Illinois
Ann & Robert H Lurie Children's Hospital of Chicago
Chicago

United States, Massachusetts
Boston Children's Hospital
Boston

United States, Michigan
Karmanos Cancer Institute
Detroit

United States, New York
Weill Cornell Medical College
New York

United States, Ohio
Cleveland Clinic
Cleveland

United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia

United States, Tennessee
Vanderbilt - Ingram Cancer Center
Nashville

United States, Texas
The University of Texas - MD Anderson Cancer Center
Houston

Australia, Queensland
Mater Hospital Brisbane
South Brisbane

Australia, South Australia
Royal Adelaide Hospital
Adelaide

Australia, Victoria
Monash Medical Centre
Clayton

Australia
Royal Prince Alfred Hospital
Camperdown

Australia
Prince of Wales Hospital
Randwick

Belgium
Algemeen Ziekenhuis Klina
Brasschaat

Belgium
AZ Sint-Jan AV Brugge
Brugge

Belgium
Universitair Ziekenhuis Gent
Ghent

Belgium
UZ Leuven
Leuven

Bulgaria
University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
Plovdiv

Bulgaria
Specialized Hospital for Active Treatment of Haematological Diseases - Sofia
Sofia

Bulgaria
Multiprofile Hospital for Active Treatment Sveta Marina EAD
Varna

Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto

Canada, Ontario
University Health Network
Toronto

Canada, Ontario
Princess Margaret Cancer Centre
Toronto

Germany
Medizinisches Versorgungszentrum (MVZ) Onkologischer Schwerpunkt am Oskar-Helene-Heim
Berlin

Germany
Universitatsklinikum Carl Gustav Carus an der TU Dresden
Dresden

Germany
Universitaetsklinikum Duesseldorf
Duesseldorf

Germany
Marien Hospital
Dusseldorf

Germany
Universitatsklinikum Halle Saale
Halle

Germany
OncoResearch Lerchenfeld GmbH
Hamburg

Germany
Medizinische Hochschule Hannover
Hannover

Germany
Universitatsklinikum Leipzig
Leipzig

Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz

Germany
Klinikum rechts der Isar der Technischen Universitaet Muenchen
München

Greece
Aghia Sophia' Children's General Hospital of Athens
Athens

Greece
Laiko General Hospital of Athens - Center of Thalassemia
Athens

Greece
General Hospital Georgios Gennimatas of Athens
Athens

Greece
University General Hospital of Patras
Rio Patras

Greece
General Hospital of Thessaloniki Hippokration
Thessaloniki

Israel
HaEmek Medical Center
Afula

Israel
Rambam Health Corporation
Haifa

Israel
Shaare Zedek Medical Center
Jerusalem

Israel
Hadassah Medical Center
Jerusalem

Israel
Galilee Medical Center
Nahariya

Israel
Rabin Medical Center
Petah Tikva

Italy
Azienda Ospedaliera Santi Antonio Biagio E Cesare Arrigo
Allessandria

Italy
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola Malpighi
Bologna

Italy
Presidio Ospedaliero Antonio Perrino
Brindisi

Italy
Azienda Sanitaria Locale (ASL) Cagliari - Ospedale Regionale per le Microcitemie
Cagliari

Italy
Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna
Ferrara

Italy
Azienda Ospedaliera Universitaria Careggi
Firenze

Italy
Azienda Ospedaliera Universitaria Careggi
Firenze

Italy
Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite
Genoa

Italy
Presidio Ospedaliero Vito Fazzi
Lecce

Italy
Maggiore Polyclinic Hospital, IRCCS Ca' Granda
Milano

Italy
Azienda Ospedaliero Universitaria Di Modena Policlinico
Modena

Italy
AORN A Cardarelli
Napoli

Italy
AOU dell'Università degli Studi della Campania Luigi Vanvitelli
Napoli

Italy
Azienda Ospedaliero Universitaria S. Luigi Gonzaga
Orbassano

Italy
IRCCS Policlinico San Matteo
Pavia

Italy
Azienda Ospedaliera Bianchi Melacrino Morelli
Reggio Di Calabria

Italy
Fondazione PTV Policlinico Tor Vergata
Roma

Italy
Istituto Clinico Humanitas
Rozzano

Italy
Ospedale di Circolo di Varese
Varese

Italy
Azienda Ospedaliera Universitaria Integrata Di Verona
Verona

Lebanon
Chronic Care Center
Hazmieh

Malaysia, Johor
Hospital Sultanah Aminah
Johor Bahru

Malaysia, Kedah
Hospital Sultanah Bahiyah
Alor Setar

Malaysia, Perak
Hospital Raja Permaisuri Bainun
Ipoh

Malaysia, Sabah
Queen Elizabeth Hospital
Kota Kinabalu

Malaysia, Sarawak
Hospital Umum Sarawak
Kuching

Malaysia, Wilayah Persekutuan Kuala Lumpur
University Malaya Medical Centre
Kuala Lumpur

Netherlands
Vrije Universiteit Medisch Centrum (VUMC)
Amsterdam

Spain
Hospital Universitario Cruces
Barakaldo

Spain
Hospital Universitari Vall d'Hebron
Barcelona

Spain
Instituto Catalan de Oncologia-Hospital Duran i Reynals
Barcelona

Spain
Hospital General Universitario Gregorio Marañon
Madrid

Spain
Hospital Universitario Central de Asturias
Oviedo

Spain
Universitario de Salamanca - Hospital Clinico
Salamanca

Spain
Hospital Universitario Virgen del Rocio
Seville

Spain
Hospital Universitari i Politecnic La Fe de Valencia
Valencia

Sweden
Sahlgrenska Universitetssjukhuset
Goteborg

Sweden
Skanes Universitetssjukhus Lund
Lund

Sweden
Karolinska Universitetssjukhuset - Huddinge
Stockholm

Taiwan
Kaohsiung Medical University Hospital
Kaohsiung, San Ming Dist.

Taiwan
China Medical University Hospital
Taichung

Taiwan
National Taiwan University Hospital
Taipei, Zhongzheng Dist.

Thailand
Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital
Bangkok

Thailand
Siriraj Hospital Mahidol University
Bangkok

Thailand
Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital
Chiang Mai

Tunisia
University Hospital Farhat Hached
Sousse

Tunisia
Bone Marrow Transplant Center
Tunis

Tunisia
Aziza Othmana Hospital
Tunis

Tunisia
Military Hospital of Tunis
Tunis

Turkey
Acibadem Adana Hospital
Adana

Turkey
Ankara University Medical Faculty Cebeci Hospital
Ankara

Turkey
Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
Istanbul

Turkey
Istanbul University Cerrahpasa Medical Faculty Hospital
Istanbul

Turkey
Ege Universitesi Tip Fakultesi Hastanesi
Izmir

Turkey
Mersin University Medical Faculty
Mersin

United Kingdom
Aberdeen Royal Infirmary
Aberdeen

United Kingdom
The Leeds Teaching Hospitals NHS Trust - St James's University Hospital
Leeds

United Kingdom
Barts Health NHS Trust - The Royal London Hospital
London

United Kingdom
Whittington Hospital
London

United Kingdom
University College London Hospitals NHS Foundation Trust - University College Hospital
London

United Kingdom
Kings College Hospital
London

United Kingdom
Oxford University Hospitals NHS Foundation Trust-Churchill Hospital-Cancer and Haematology Centre
Oxford

United Kingdom
Kings Mill Hospital
Sutton in Ashfield

Sponsors and Collaborators

Celgene

Investigators

Study Director: Rodrigo Ito, M.D. Celgene Corporation

More Information

  • Responsible Party: Celgene
  • ClinicalTrials.gov Identifier: NCT04064060 History of Changes
  • Other Study ID Numbers: ACE-536-LTFU-001, U1111-1235-8123, 2018-002915-93
  • First Posted: August 21, 2019 Key Record Dates
  • Last Update Posted: December 1, 2020
  • Last Verified: November 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:

  • Plan to Share IPD: Yes
  • Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
  • Supporting Materials: Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), Analytic Code
  • Time Frame: See Plan Description
  • Access Criteria: See Plan Description
  • URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Celgene: ACE-536
    MDS
    Myeloproliferative neoplasm (MPN)-associated myelofibrosis
    Beta-thalassemia
    Luspatercept
  • Additional relevant MeSH terms: Myelodysplastic Syndromes
    Preleukemia
    Primary Myelofibrosis
    Thalassemia
    Myeloproliferative Disorders
    beta-Thalassemia