Clinical trial NCT04064060: A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Myelodysplastic Syndromes (MDS)
Beta-thalassemia
Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis
Keywords: ACE-536
Luspatercept
MDS
Beta-thalassemia
Myeloproliferative neoplasm (MPN)-associated myelofibrosis
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2019-08-21
Enrollment: 665
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 ACE-536-LTFU-001 rollover study will be terminated, and relevant participants will discontinue from the study when all participants fulfill 5 years on the study, including treatment and follow-up.


Eligibility criteria: Inclusion Criteria:

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

1. Participant is ≥ 18 years at the time of signing the informed consent form (ICF).
2. Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
3. 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:

   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 LTPTFU 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. Participant understands and voluntarily signs an informed consent document prior to any study-related assessments or procedures being conducted.
5. Participant demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.
6. Applies to on treatment Participants 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) 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 participant practices true abstinence from heterosexual contact.
2. Agrees 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 participants only- Male participants must:

a. Agrees 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:

1. Applies to on treatment participants only- Concomitant use of any medications/procedures that are prohibited in the parent luspatercept protocol.
2. Participant has met one or more criteria for study discontinuation as stipulated in the parent luspatercept protocol.
3. 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.
4. Applies to on treatment participants only- Pregnant or breastfeeding females.
5. 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.
6. 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.
7. Participant has any condition that confounds the ability to interpret data from the study.

Primary outcomes:
measure: Adverse Events (AEs)
timeFrame: From enrollment until at least 42 Day Safety Follow-up Phase
measure: Number of participants progressing to high/very high risk MDS or AML.
timeFrame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
measure: Percentage of participants progressing to high/very high risk MDS or AML
timeFrame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
measure: Number of participants developing other malignancies/pre-malignancies
timeFrame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
measure: Percentage of participants developing other malignancies/pre-malignancies
timeFrame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Secondary outcomes:
measure: Overall Survival
timeFrame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
measure: Number of participants developing treatment emergent extramedullary hematopoiesis (EMH) masses
timeFrame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
measure: Percentage of participants developing treatment emergent EMH masses
timeFrame: Enrollment to Long-term post-treatment follow-up (Approximately, 5 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles RHU
state: California
city: Oakland
country: United States
facility: Local Institution - 971
state: California
city: Stanford
country: United States
facility: Local Institution - 978
state: California
city: Tampa
country: United States
facility: Local Institution - 975
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Local Institution - 961
state: Michigan
city: New York
country: United States
facility: Local Institution - 969
state: New York
city: Cleveland
country: United States
facility: Local Institution - 967
state: Ohio
city: Philadelphia
country: United States
facility: Local Institution - 972
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas - MD Anderson Cancer Center
state: Texas
city: South Brisbane
country: Australia
facility: Local Institution - 100
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Local Institution - 102
state: Victoria
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Brasschaat
country: Belgium
facility: Local Institution - 182
city: Brugge
country: Belgium
facility: Local Institution - 180
city: Ghent
country: Belgium
facility: Local Institution - 183
city: Leuven
country: Belgium
facility: Local Institution - 184
city: Boulevard
country: Bulgaria
facility: Local Institution - 220
state: Sofia
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
city: Toronto
country: Canada
facility: Local Institution - 262
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 263
state: Ontario
city: Beijing
country: China
facility: Local Institution - 131
state: Beijing
city: Guangzhou
country: China
facility: Local Institution - 135
state: Guangdong
city: Shanghai
country: China
facility: Local Institution - 132
state: Shanghai
city: Chengdu
country: China
facility: Local Institution - 134
state: Sichuan
city: Tianjin
country: China
facility: Local Institution - 130
state: Tianjin
city: Hangzhou
country: China
facility: Local Institution - 133
state: Zhejiang
city: Angers
country: France
facility: Local Institution - 305
city: Creteil
country: France
facility: Local Institution - 300
city: La Tronche
country: France
facility: Local Institution - 310
city: Lille
country: France
facility: Local Institution - 306
city: Marseille Cedex 9
country: France
facility: Local Institution - 301
city: Paris
country: France
facility: Local Institution - 302
city: Pessac Cedex
country: France
facility: Local Institution - 307
city: Pierre Benite cedex
country: France
facility: Local Institution - 304
city: Strasbourg
country: France
facility: Local Institution - 308
city: Toulouse Cedex 9
country: France
facility: Local Institution - 309
city: Tours
country: France
facility: Local Institution - 303
city: Berlin
country: Germany
facility: Local Institution - 341
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus an der TU Dresden
city: Duesseldorf
country: Germany
facility: Local Institution - 345
city: Dusseldorf
country: Germany
facility: Local Institution - 346
city: Halle
country: Germany
facility: Local Institution - 343
city: Hamburg
country: Germany
facility: Local Institution - 342
city: Hannover
country: Germany
facility: Local Institution - 344
city: Leipzig
country: Germany
facility: Local Institution - 349
city: Mainz
country: Germany
facility: Local Institution - 340
city: München
country: Germany
facility: Klinikum Rechts der Isar der Technischen Universitaet Muenchen
city: Athens
country: Greece
facility: Aghia Sophia' Children's General Hospital of Athens
city: Athens
country: Greece
facility: Laiko General Hospital of Athens - Center of Thalassemia
city: Athens
country: Greece
facility: Local Institution - 384
city: Rio Patras
country: Greece
facility: Local Institution - 383
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki Hippokration
city: Afula
country: Israel
facility: Local Institution - 425
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Jerusalem
country: Israel
facility: Local Institution - 422
city: Jerusalem
country: Israel
facility: Local Institution - 424
city: Nahariya
country: Israel
facility: Local Institution - 421
city: Petah Tikva
country: Israel
facility: Local Institution - 423
city: Firenze
country: Italy
facility: Local Institution - 478
state: Toscana
city: Firenze
country: Italy
facility: Local Institution - 471
state: Toscana
city: Allessandria
country: Italy
facility: Local Institution - 470
city: Bologna
country: Italy
facility: Local Institution - 464
city: Brindisi
country: Italy
facility: Local Institution - 466
city: Cagliari
country: Italy
facility: Local Institution - 477
city: Ferrara
country: Italy
facility: Local Institution - 462
city: Genoa
country: Italy
facility: Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite
city: Lecce
country: Italy
facility: Local Institution - 473
city: Milano
country: Italy
facility: Maggiore Polyclinic Hospital, IRCCS Ca' Granda
city: Modena
country: Italy
facility: Local Institution - 479
city: Napoli
country: Italy
facility: AORN A Cardarelli
city: Napoli
country: Italy
facility: AOU dell'Universita degli Studi della Campania Luigi Vanvitelli
city: Orbassano
country: Italy
facility: Azienda Ospedaliero Universitaria S. Luigi Gonzaga
city: Pavia
country: Italy
facility: Local Institution - 469
city: Reggio Di Calabria
country: Italy
facility: Local Institution - 468
city: Roma
country: Italy
facility: Local Institution - 465
city: Rozzano
country: Italy
facility: Local Institution - 474
city: Varese
country: Italy
facility: Ospedale di Circolo di Varese
city: Verona
country: Italy
facility: Local Institution - 463
city: Nagoya
country: Japan
facility: Local Institution - 610
state: Aichi
city: Kamogawa
country: Japan
facility: Local Institution - 601
state: Chiba
city: Matsuyama
country: Japan
facility: Matsuyama Red Cross Hospital
state: Ehime
city: Ogaki
country: Japan
facility: Ogaki Municipal Hospital
state: Gifu
city: Himeji
country: Japan
facility: Japanese Red Cross Society Himeji Hospital
state: Hyogo
city: Hitachi
country: Japan
facility: Local Institution - 605
state: Ibaraki
city: Sagamihara
country: Japan
facility: Kitasato University Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Local Institution - 0979
state: Miyagi
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Nagasaki-shi
country: Japan
facility: Local Institution - 611
state: Nagasaki
city: Shibuya City
country: Japan
facility: Japanese Red Cross Medical Center
state: Tokyo
city: Shinagawa City
country: Japan
facility: NTT Medical Center Tokyo
state: Tokyo
city: Chiba
country: Japan
facility: Local Institution - 612
city: Kamakura
country: Japan
facility: Shonan Kamakura General Hospital
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Osaka
country: Japan
facility: Local Institution - 604
city: Hazmieh
country: Lebanon
facility: Chronic Care Center
city: Johor Bahru
country: Malaysia
facility: Local Institution - 545
state: Johor
city: Alor Setar
country: Malaysia
facility: Hospital Sultanah Bahiyah
state: Kedah
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
state: Perak
city: Kota Kinabalu
country: Malaysia
facility: Queen Elizabeth Hospital
state: Sabah
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
state: Sarawak
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
state: Wilayah Persekutuan Kuala Lumpur
city: Amsterdam
country: Netherlands
facility: Local Institution - 580
city: Barakaldo
country: Spain
facility: Local Institution - 681
city: Barcelona
country: Spain
facility: Local Institution - 686
city: Barcelona
country: Spain
facility: Local Institution - 685
city: Madrid
country: Spain
facility: Local Institution - 687
city: Oviedo
country: Spain
facility: Local Institution - 682
city: Salamanca
country: Spain
facility: Local Institution - 684
city: Seville
country: Spain
facility: Local Institution - 680
city: Valencia
country: Spain
facility: Local Institution - 683
city: Goteborg
country: Sweden
facility: Local Institution - 720
city: Lund
country: Sweden
facility: Local Institution - 722
city: Stockholm
country: Sweden
facility: Local Institution - 721
city: Kaohsiung, San Ming Dist.
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: Local Institution - 761
city: Bangkok
country: Thailand
facility: Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital Mahidol University
city: Chiang Mai
country: Thailand
facility: Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital
city: Sousse
country: Tunisia
facility: University Hospital Farhat Hached
city: Tunis
country: Tunisia
facility: Bone Marrow Transplant Center
city: Tunis
country: Tunisia
facility: Aziza Othmana Hospital
city: Tunis
country: Tunisia
facility: Military Hospital of Tunis
city: Adana
country: Turkey
facility: Acibadem Adana Hospital
city: Ankara
country: Turkey
facility: Local Institution - 885
city: Istanbul
country: Turkey
facility: Local Institution - 882
city: Istanbul
country: Turkey
facility: Local Institution - 884
city: Izmir
country: Turkey
facility: Local Institution - 880
city: Mersin
country: Turkey
facility: Local Institution - 883
city: Aberdeen
country: United Kingdom
facility: Local Institution - 925
city: Leeds
country: United Kingdom
facility: Local Institution - 921
city: London
country: United Kingdom
facility: Local Institution - 923
city: London
country: United Kingdom
facility: Whittington Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust - University College Hospital
city: London
country: United Kingdom
facility: Local Institution - 928
city: London
country: United Kingdom
facility: Kings College Hospital
city: Oxford
country: United Kingdom
facility: Local Institution - 929
city: Sutton in Ashfield
country: United Kingdom
facility: Local Institution - 926
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: