Clinical trial • Phase III • Haematology

Luspatercept for Myelodysplastic syndrome | Beta thalassemia | Myelofibrosis

Phase III trial of Luspatercept for Myelodysplastic syndrome | Beta thalassemia | Myelofibrosis. open-label. 154 participants.

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Myelodysplastic syndrome | Beta thalassemia | Myelofibrosis
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
22-12-2023
First CTIS Authorization Date
20-02-2024

Trial design

open-label Phase III trial in Greece, Italy, Germany and others.

Open Label
Yes
Target Sample Size
154
Trial Duration For Participant
360

Eligibility

Recruits 154 Vulnerable populations are considered by local regulations and subjects considered vulnerable (eg, imprisoned or institutionalized) are excluded. All participants must be ≥ 18 and must understand and voluntarily sign an informed consent document prior to any study-related assessments or procedures; no procedures for assent are described (minors are excluded)..

Pregnancy Exclusion
4) Applies to on treatment subjects only- Pregnant or breastfeeding females. If breastfeeding, agree to stop breastfeeding prior to the participation in the study and not to resume breastfeeding during treatment with luspatercept and until 3 months after the last dose.
Vulnerable Population
Vulnerable populations are considered by local regulations and subjects considered vulnerable (eg, imprisoned or institutionalized) are excluded. All participants must be ≥ 18 and must understand and voluntarily sign an informed consent document prior to any study-related assessments or procedures; no procedures for assent are described (minors are excluded).

Inclusion criteria

  • {"criterion_text":"- 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).\n- 2) Subject is willing and able to adhere to the study visit schedule and other protocol requirements.\n- 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: a) Assigned to luspatercept treatment, continues to receive clinical benefit in the opinion of the investigator and should continue to receive luspatercept treatment, OR b) 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 c) 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 Posttreatment Follow-up Phase in the rollover study until the follow-up commitments are met (unless requirements are met as per parent protocol to cross over to luspatercept treatment).\n- 4) Subject understands and voluntarily signs an informed consent document prior to any studyrelated assessments or procedures being conducted.\n- 5) Subject demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.\n- 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 or amenorrhea due to other medical reasons 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: a) Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. A medically supervised serum pregnancy test (conducted locally) is to be obtained and verified negative in all female subjects of childbearing potential at enrollment (for details refer to Section 6.1.7). 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. b) 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.\n- 7) Applies to on treatment subjects only- Male subjects must: a) 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

  • {"criterion_text":"- 1) Applies to on treatment subjects only- Concomitant use of any medications/procedures that are prohibited in the parent luspatercept protocol.\n- 2) Subject has met one or more criteria for study discontinuation as stipulated in the parent luspatercept protocol.\n- 3) Applies to on treatment subjects only- More than 26 days between last luspatercept dose in the parent protocol and first dose into ACE-536-LTFU-001 protocol unless dose delay or dose discontinuation criteria met.\n- 4) Applies to on treatment subjects only- Pregnant or breastfeeding females. If breastfeeding, agree to stop breastfeeding prior to the participation in the study and not to resume breastfeeding during treatment with luspatercept and until 3 months after the last dose.\n- 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.\n- 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.\n- 7) Subject has any condition that confounds the ability to interpret data from the study."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Adverse events (AEs)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Progression to high/very high-risk myelodysplastic syndrome (MDS)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Progression to Acute myeloid leukemia (AML) (MDS and myelofibrosis [MF] only)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Development of other malignancies/premalignancies","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Overall survival","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Treatment-emergent EMH masses","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
154
Recruitment Window Months
115
Consent Approach
Informed consent must be provided voluntarily by the subject prior to any study-related assessments (subjects must understand and sign an ICF). All participants are adults (≥18). Multiple ICF and information documents exist (on-treatment and follow-up versions, pregnancy/partner forms). Available ICF/document languages in the application include: English, Greek, Spanish, French, German, Bulgarian, Italian, Swedish (country-specific ICFs and translations are listed in the public documents). No assent process is described because minors are excluded.

Geography

Total Number Of Sites
20
Total Number Of Participants
139

Greece

Earliest CTIS Part Ii Submission Date
22-03-2024
Latest Decision Or Authorization Date
17-12-2025
Processing Time Days
635
Number Of Sites
3
Number Of Participants
44

Sites

Site Name
Nosokomeio Paidon I Agia Sofia
Department Name
Thalassemia Unit, Division of Pediatric Hematology-Oncology 1st Department of Pediatrics
Contact Person Name
Antonis Kattamis
Contact Person Email
ankatt@med.uoa.gr
Site Name
Ippokratio General Hospital Of Thessaloniki
Department Name
Thalassaemia Unit
Contact Person Name
Efthymia Vlachaki
Contact Person Email
efivlachaki@yahoo.gr
Site Name
Laiko General Hospital Of Athens
Department Name
Centre of Thalassaemia
Contact Person Name
Maria Dimopoulou
Contact Person Email
mdimfish@hotmail.com

Italy

Earliest CTIS Part Ii Submission Date
23-02-2024
Latest Decision Or Authorization Date
22-12-2025
Processing Time Days
668
Number Of Sites
7
Number Of Participants
66

Sites

Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
Dipartimento di Medicina Interna e Specializzazioni Mediche
Contact Person Name
Maria Domenica Cappellini
Contact Person Email
maria.cappellini@unimi.it
Site Name
Ente Ospedaliero Ospedali Galliera Di Genova
Department Name
S.S.D. Microcitemia, Anemie Congenite e Dismetabolismo del Ferro
Contact Person Name
Manuela Balocco
Contact Person Email
manuela.balocco@galliera.it
Site Name
Careggi University Hospital
Department Name
" Centro di Ricerca e Innovazione per le Malattie Mieloproliferative (CRIMM) Dipartimento di Medici
Contact Person Name
Alessandro Maria Vannucchi
Contact Person Email
amvannucchi@unifi.it
Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
DAI Materno-Infantile Ematologia ed Oncologia Pediatrica
Contact Person Name
Silverio Perrotta
Site Name
Grande Ospedale Metropolitano Bianchi Melacrino Morelli
Department Name
U.O.C. di Ematologia
Contact Person Name
Caterina Alati
Contact Person Email
caterina.alati@gmail.com
Site Name
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
Department Name
UOSD Malattie Rare del Globulo Rosso
Contact Person Name
Paolo Ricchi
Contact Person Email
paolo.ricchi@aocardarelli.it
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
S.C.D.U. Microcitemie-Pediatria
Contact Person Name
Giovanni Battista Ferrero

Germany

Earliest CTIS Part Ii Submission Date
22-02-2024
Latest Decision Or Authorization Date
14-03-2025
Processing Time Days
386
Number Of Sites
4
Number Of Participants
8

Sites

Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
III. Medizinische Klinik
Contact Person Name
Katharina Götze
Contact Person Email
k.goetze@lrz.tu-muenchen.de
Site Name
Universitaetsklinikum Halle (Saale) AöR
Department Name
Klinik für Innere Medizin IV, Haematologie/Onkologie/Haemostaseologie
Contact Person Name
Haifa Al-Ali
Contact Person Email
haifa.al-ali@uk-halle.de
Site Name
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
Department Name
Medizinische Klinik I
Contact Person Name
Katja Sockel
Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
III. Med. Klinik der Johannes Gutenberg-Universitaet
Contact Person Name
Daniel Sasca

France

Earliest CTIS Part Ii Submission Date
26-02-2024
Latest Decision Or Authorization Date
13-03-2025
Processing Time Days
381
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Assistance Publique Hopitaux De Paris
Department Name
Hématologie Seniors
Contact Person Name
Pierre Fenaux
Contact Person Email
pierre.fenaux@aphp.fr

Bulgaria

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
12-03-2025
Processing Time Days
385
Number Of Sites
2
Number Of Participants
13

Sites

Site Name
University Multiprofile Hospital For Active Treatment Saint Georgi EAD
Department Name
Clinic of Clinical Hematology
Contact Person Name
Pencho Georgiev
Contact Person Email
penchogeorgiev@yahoo.com
Site Name
Specialized Hospital For Active Treatment Of Hematological Diseases EAD
Department Name
Clinic of Clinical Hematology
Contact Person Name
Penka Ganeva
Contact Person Email
ganevapenka@yahoo.com

Netherlands

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
21-02-2024
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Amsterdam UMC
Department Name
Department of Hematology
Contact Person Name
Arjan van de Loosdrecht
Contact Person Email
hematology@amsterdamumc.nl

Sweden

Earliest CTIS Part Ii Submission Date
20-02-2024
Latest Decision Or Authorization Date
12-03-2025
Processing Time Days
386
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Sahlgrenska University Hospital-Vastra Gotalandsregionen
Department Name
Internal Medicine
Contact Person Name
Lena Von Bahr
Contact Person Email
lena.von.bahr@vgregion.se

Sponsor

Primary sponsor

Full Name
Celgene Corp.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
PPD Development LP
Responsibilities
["1","10","11","12","6","7"]

Third parties

  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"[\"1\",\"10\",\"11\",\"12\",\"6\",\"7\"]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"[\"7\"]","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Endpoint, IVRS Central Management - IMSC","duties_or_roles":"[{\"code\":\"15\",\"value\":\"Patient registration, IP supply\"}]","organisation_type":"Industry"}

Investigational products

Investigational Product Name
Reblozyl 75 mg powder for solution for injection
Active Substance
Luspatercept
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS USE
Route
Subcutaneous
Authorisation Status
Marketing authorisation present
Orphan Designation
Yes
Maximum Dose
1.75 mg/kg (max daily); max total dose amount 152 mg/kg
Investigational Product Name
Reblozyl 25 mg powder for solution for injection
Active Substance
Luspatercept
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS USE
Route
Subcutaneous
Authorisation Status
Marketing authorisation present
Orphan Designation
Yes
Maximum Dose
1.75 mg/kg (max daily); max total dose amount 152 mg/kg

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