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

Sponsor

Celgene (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04064060

Collaborator

(none)

665

Enrollment

141

Locations

Arm

127.4

Anticipated Duration (Months)

4.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept, to the following participants:

Participants 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 from continuing treatment with luspatercept
Participants 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
The study design is divided into the Transition Phase, Treatment Phase and Follow-up Phase. Participants 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 is defined as one Enrollment visit
Treatment Phase: For participants 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. This does not apply to participants that are in long-term follow-up from the parent protocol
Follow-up Phase includes:
42 Day Safety Follow-up Visit
During the Safety Follow up, the participants 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
Participants will be followed for overall survival every 6 months for at least 5 years from first dose of luspatercept in the parent protocol, or 3 years of post-treatment from last dose, whichever occurs later, or until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. Participants 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

Participants 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 participants will discontinue from the study when all participants fulfill at least 5 years from the first dose of luspatercept in the parent protocol, or 3 years of post-treatment from last dose, whichever occurs later.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

665 participants

Allocation:

N/A

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 :

Aug 12, 2019

Anticipated Primary Completion Date :

Mar 25, 2030

Anticipated Study Completion Date :

Mar 25, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ACE-536 Luspatercept will be administered as a subcutaneous (SC) injection to participants 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 Other Names: ACE-536

Arm

Intervention/Treatment

Experimental: ACE-536

Luspatercept will be administered as a subcutaneous (SC) injection to participants 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

Other Names:

ACE-536

Outcome Measures

Primary Outcome Measures

Adverse Events (AEs) [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
Number of participants progressing to high/very high risk MDS or AML. [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).
Percentage of participants progressing to high/very high risk MDS or AML [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)
Number of participants developing other malignancies/pre-malignancies [Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)]
Development of other malignancies/pre-malignancies
Percentage of participants developing other malignancies/pre-malignancies [Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)]
Development of other malignancies/pre-malignancies

Secondary Outcome Measures

Overall Survival [Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)]
Time from date of randomization until death from any cause
Number of participants developing treatment emergent extramedullary hematopoiesis (EMH) masses [Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)]
Percentage of participants developing treatment emergent EMH masses [Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Participant is ≥ 18 years at the time of signing the informed consent form (ICF).
Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
Participant has been participating in a luspatercept trial and continues to fulfill all the requirements of the parent protocol and the participant has been either:
Assigned to luspatercept treatment, continues to receive clinical benefit in the opinion of the investigator and should continue to receive luspatercept treatment, OR
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
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).
Participant understands and voluntarily signs an informed consent document prior to any study-related assessments or procedures being conducted.
Participant demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.
Applies to on treatment Participants only- females of childbearing potential (FCBP) defined as a sexually mature woman who:

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:

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 participant 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 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.
Applies to on treatment participants only- Male participants must:

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 participant from enrollment:

Applies to on treatment participants only- Concomitant use of any medications/procedures that are prohibited in the parent luspatercept protocol.
Participant has met one or more criteria for study discontinuation as stipulated in the parent luspatercept protocol.
Applies to on treatment participants 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.
Applies to on treatment participants only- Pregnant or breastfeeding females.
Participant 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.
Participant 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.
Participant has any condition that confounds the ability to interpret data from the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital Los Angeles RHU	Los Angeles	California	United States	90027-6062
2	UCSF Benioff Children's Hospital Oakland	Oakland	California	United States	94609
3	Stanford Cancer Center	Stanford	California	United States	94305
4	Moffitt Cancer Center	Tampa	Florida	United States	33612
5	Moffitt Cancer Center	Tampa	Florida	United States	33612
6	Ann & Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
7	Boston Children's Hospital	Boston	Massachusetts	United States	02115
8	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
9	Weill Cornell Medical College	New York	New York	United States	10065
10	Cleveland Clinic	Cleveland	Ohio	United States	44195
11	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
12	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee	United States	37232-5505
13	The University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
14	Mater Hospital Brisbane	South Brisbane	Queensland	Australia	4101
15	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
16	Monash Medical Centre	Clayton	Victoria	Australia	3168
17	Royal Prince Alfred Hospital	Camperdown		Australia	2050
18	Prince of Wales Hospital	Randwick		Australia	2031
19	Algemeen Ziekenhuis Klina	Brasschaat		Belgium	2930
20	AZ Sint-Jan AV Brugge	Brugge		Belgium	8000
21	Local Institution - 183	Ghent		Belgium	9000
22	Universitair Ziekenhuis Gent	Ghent		Belgium	9000
23	UZ Leuven	Leuven		Belgium	3000
24	Local Institution - 220	Boulevard	Sofia	Bulgaria	1797
25	University Multiprofile Hospital for Active Treatment Sveti Georgi EAD	Plovdiv		Bulgaria	4002
26	Specialized Hospital for Active Treatment of Haematological Diseases - Sofia	Sofia		Bulgaria	1756
27	Multiprofile Hospital for Active Treatment Sveta Marina EAD	Varna		Bulgaria	9010
28	Local Institution - 262	Toronto	Ontario	Canada	M4N 3M5
29	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
30	University Health Network	Toronto	Ontario	Canada	M5G 2C4
31	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
32	CHU d'Angers	Angers		France	49033
33	Local Institution - 305	Angers		France	49033
34	Hopital Henri Mondor	Creteil		France	94010
35	Centre Hospitalier Universitaire de Grenoble Hopital Albert Michallon	La Tronche		France	38700
36	CHRU de Lille-Hopital Claude Huriez	Lille		France	59037
37	Local Institution - 306	Lille		France	59037
38	Hopitaux de La Timone	Marseille Cedex 9		France	13385
39	Hopital Saint Louis	Paris		France	75010
40	Local Institution - 302	Paris		France	75010
41	Hopital Haut Leveque	Pessac Cedex		France	33604
42	Centre Hospitalier Lyon Sud	Pierre Benite cedex		France	69495
43	Hopital civil	Strasbourg		France	67091
44	Institut Universitaire du Cancer de Toulouse - Oncopole	Toulouse Cedex 9		France	31059
45	Hopital Bretonneau	Tours		France	37044
46	Medizinisches Versorgungszentrum (MVZ) Onkologischer Schwerpunkt am Oskar-Helene-Heim	Berlin		Germany	14195
47	Local Institution - 348	Dresden		Germany	01307
48	Universitatsklinikum Carl Gustav Carus an der TU Dresden	Dresden		Germany	01307
49	Universitaetsklinikum Duesseldorf	Duesseldorf		Germany	40225
50	Marien Hospital	Dusseldorf		Germany	40479
51	Universitatsklinikum Halle Saale	Halle		Germany	06120
52	Local Institution - 342	Hamburg		Germany	22081
53	OncoResearch Lerchenfeld GmbH	Hamburg		Germany	22081
54	Medizinische Hochschule Hannover	Hannover		Germany	30625
55	Universitatsklinikum Leipzig	Leipzig		Germany	04103
56	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz		Germany	55131
57	Klinikum rechts der Isar der Technischen Universitaet Muenchen	München		Germany	81675
58	Aghia Sophia' Children's General Hospital of Athens	Athens		Greece	115 27
59	Laiko General Hospital of Athens - Center of Thalassemia	Athens		Greece	115 27
60	General Hospital Georgios Gennimatas of Athens	Athens		Greece	11527
61	University General Hospital of Patras	Rio Patras		Greece	26500
62	General Hospital of Thessaloniki Hippokration	Thessaloniki		Greece	54642
63	Local Institution - 381	Thessaloniki		Greece	54642
64	HaEmek Medical Center	Afula		Israel	18341
65	Rambam Health Corporation	Haifa		Israel	3109601
66	Shaare Zedek Medical Center	Jerusalem		Israel	91031
67	Hadassah Medical Center	Jerusalem		Israel	91120
68	Galilee Medical Center	Nahariya		Israel	22100
69	Rabin Medical Center	Petah Tikva		Israel	49100
70	Azienda Ospedaliera Santi Antonio Biagio E Cesare Arrigo	Allessandria		Italy	15100
71	Local Institution - 470	Allessandria		Italy	15100
72	Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola Malpighi	Bologna		Italy	40138
73	Presidio Ospedaliero Antonio Perrino	Brindisi		Italy	72100
74	Azienda Sanitaria Locale (ASL) Cagliari - Ospedale Regionale per le Microcitemie	Cagliari		Italy	09121
75	Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna	Ferrara		Italy	44124
76	Azienda Ospedaliera Universitaria Careggi	Firenze		Italy	50134
77	Azienda Ospedaliera Universitaria Careggi	Firenze		Italy	50134
78	Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite	Genoa		Italy	16128
79	Local Institution - 473	Lecce		Italy	73100
80	Presidio Ospedaliero Vito Fazzi	Lecce		Italy	73100
81	Maggiore Polyclinic Hospital, IRCCS Ca' Granda	Milano		Italy	20122
82	Azienda Ospedaliero Universitaria Di Modena Policlinico	Modena		Italy	41100
83	AORN A Cardarelli	Napoli		Italy	80131
84	AOU dell'Università degli Studi della Campania Luigi Vanvitelli	Napoli		Italy	80131
85	Azienda Ospedaliero Universitaria S. Luigi Gonzaga	Orbassano		Italy	10043
86	IRCCS Policlinico San Matteo	Pavia		Italy	27100
87	Azienda Ospedaliera Bianchi Melacrino Morelli	Reggio Di Calabria		Italy	89124
88	Local Institution - 468	Reggio Di Calabria		Italy	89124
89	Fondazione PTV Policlinico Tor Vergata	Roma		Italy	133
90	Istituto Clinico Humanitas	Rozzano		Italy	20089
91	Ospedale di Circolo di Varese	Varese		Italy	21100
92	Azienda Ospedaliera Universitaria Integrata Di Verona	Verona		Italy	37134
93	Local Institution - 603	Sagamihara	Kanagawa	Japan	252-0329
94	Local Institution - 0979	Sendai	Miyagi	Japan	980-8574
95	Local Institution - 600	Shinagawa City	Tokyo	Japan	141-8625
96	Local Institution - 611	Nagasaki		Japan	852-8511
97	Chronic Care Center	Hazmieh		Lebanon	1003
98	Hospital Sultanah Aminah	Johor Bahru	Johor	Malaysia	80100
99	Hospital Sultanah Bahiyah	Alor Setar	Kedah	Malaysia	05460
100	Hospital Raja Permaisuri Bainun	Ipoh	Perak	Malaysia	30990
101	Queen Elizabeth Hospital	Kota Kinabalu	Sabah	Malaysia	88586
102	Hospital Umum Sarawak	Kuching	Sarawak	Malaysia	93586
103	University Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan Kuala Lumpur	Malaysia	59100
104	Vrije Universiteit Medisch Centrum (VUMC)	Amsterdam		Netherlands	1081 HV
105	Hospital Universitario Cruces	Barakaldo		Spain	48903
106	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
107	Instituto Catalan de Oncologia-Hospital Duran i Reynals	Barcelona		Spain	08908
108	Local Institution - 686	Barcelona		Spain	08908
109	Hospital General Universitario Gregorio Marañon	Madrid		Spain	28007
110	Hospital Universitario Central de Asturias	Oviedo		Spain	33011
111	Universitario de Salamanca - Hospital Clinico	Salamanca		Spain	37007
112	Hospital Universitario Virgen del Rocio	Seville		Spain	41013
113	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
114	Sahlgrenska Universitetssjukhuset	Goteborg		Sweden	413 45
115	Local Institution - 722	Lund		Sweden	SE-221 85
116	Skanes Universitetssjukhus Lund	Lund		Sweden	SE-221 85
117	Karolinska Universitetssjukhuset - Huddinge	Stockholm		Sweden	141 86
118	Kaohsiung Medical University Hospital	Kaohsiung, San Ming Dist.		Taiwan	807
119	China Medical University Hospital	Taichung		Taiwan	40447
120	National Taiwan University Hospital	Taipei, Zhongzheng Dist.		Taiwan	10002
121	Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital	Bangkok		Thailand	10330
122	Siriraj Hospital Mahidol University	Bangkok		Thailand	10700
123	Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital	Chiang Mai		Thailand	50200
124	University Hospital Farhat Hached	Sousse		Tunisia	4031
125	Bone Marrow Transplant Center	Tunis		Tunisia	1006
126	Aziza Othmana Hospital	Tunis		Tunisia	1008
127	Military Hospital of Tunis	Tunis		Tunisia	1008
128	Acibadem Adana Hospital	Adana		Turkey	01130
129	Ankara University Medical Faculty Cebeci Hospital	Ankara		Turkey	06590
130	Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi	Istanbul		Turkey	34093
131	Istanbul University Cerrahpasa Medical Faculty Hospital	Istanbul		Turkey	34098
132	Ege Universitesi Tip Fakultesi Hastanesi	Izmir		Turkey	35100
133	Mersin University Medical Faculty	Mersin		Turkey	33343
134	Aberdeen Royal Infirmary	Aberdeen		United Kingdom	AB25 2ZN
135	The Leeds Teaching Hospitals NHS Trust - St James's University Hospital	Leeds		United Kingdom	LS9 7TF
136	Barts Health NHS Trust - The Royal London Hospital	London		United Kingdom	E1 1BB
137	Whittington Hospital	London		United Kingdom	N19 5NF
138	University College London Hospitals NHS Foundation Trust - University College Hospital	London		United Kingdom	NW1 2BU
139	Kings College Hospital	London		United Kingdom	SE5 9RS
140	Oxford University Hospitals NHS Foundation Trust-Churchill Hospital-Cancer and Haematology Centre	Oxford		United Kingdom	OX3 7LE
141	Kings Mill Hospital	Sutton in Ashfield		United Kingdom	NG17 4JL