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NCT04064060PHASE3Recruiting

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

Celgene

Start Date

8/12/2019

Completion Date

5/12/2028

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

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Luspatercept

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Conditions

Myelodysplastic Syndromes (MDS)Beta-thalassemiaMyeloproliferative Neoplasm(MPN)-Associated Myelofibrosis

Locations

Local Institution - 968

Los Angeles, California 90027-6062

United States

Local Institution - 971

Oakland, California 94609

United States

Local Institution - 978

Stanford, California 94305

United States

Local Institution - 975

Tampa, Florida 33612

United States

Local Institution - 970

Chicago, Illinois 60611

United States

Local Institution - 973

Boston, Massachusetts 02115

United States

Local Institution - 961

Detroit, Michigan 48201

United States

Local Institution - 969

New York, New York 10065

United States

Local Institution - 967

Cleveland, Ohio 44195

United States

Local Institution - 972

Philadelphia, Pennsylvania 19104

United States

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee 37232-5505

United States

The University of Texas - MD Anderson Cancer Center

Houston, Texas 77030

United States

Local Institution - 100

South Brisbane, Queensland 4101

Australia

Royal Adelaide Hospital

Adelaide, South Australia 5000

Australia

Local Institution - 102

Clayton, Victoria 3168

Australia

Royal Prince Alfred Hospital

Camperdown, 2050

Australia

Local Institution - 182

Brasschaat, 2930

Belgium

Local Institution - 180

Bruges, 8000

Belgium

Local Institution - 183

Ghent, 9000

Belgium

Local Institution - 184

Leuven, 3000

Belgium

Local Institution - 220

Boulevard, Sofia 1797

Bulgaria

Local Institution - 221

Plovdiv, 4002

Bulgaria

Local Institution - 262

Toronto, Ontario M4N 3M5

Canada

Local Institution - 260

Toronto, Ontario M5G 2C4

Canada

Local Institution - 263

Toronto, Ontario M5G 2M9

Canada

Local Institution - 131

Beijing, Beijing Municipality 100730

China

Local Institution - 135

Guangzhou, Guangdong 510515

China

Local Institution - 132

Shanghai, Shanghai Municipality 200233

China

Local Institution - 134

Chengdu, Sichuan 610041

China

Local Institution - 130

Tianjin, Tianjin Municipality 300020

China

Local Institution - 133

Hangzhou, Zhejiang 310009

China

Local Institution - 305

Angers, 49033

France

Local Institution - 300

Créteil, 94010

France

Local Institution - 310

La Tronche, 38700

France

Local Institution - 306

Lille, 59037

France

Local Institution - 301

Marseille, 13385

France

Local Institution - 302

Paris, 75010

France

Local Institution - 307

Pessac, 33604

France

Local Institution - 304

Pierre-Bénite, 69495

France

Local Institution - 308

Strasbourg, 67091

France

Local Institution - 309

Toulouse, 31059

France

Local Institution - 303

Tours, 37044

France

Local Institution - 341

Berlin, 14195

Germany

Local Institution - 348

Dresden, 01307

Germany

Local Institution - 345

Düsseldorf, 40225

Germany

Local Institution - 346

Düsseldorf, 40479

Germany

Local Institution - 343

Halle, 06120

Germany

Local Institution - 342

Hamburg, 22081

Germany

Local Institution - 344

Hanover, 30625

Germany

Local Institution - 349

Leipzig, 04103

Germany

Local Institution - 340

Mainz, 55131

Germany

Local Institution - 347

München, 81675

Germany

Aghia Sophia' Children's General Hospital of Athens

Athens, 115 27

Greece

Local Institution - 380

Athens, 115 27

Greece

Local Institution - 384

Athens, 11527

Greece

Local Institution - 383

Rio Patras, 26500

Greece

Local Institution - 381

Thessaloniki, 54642

Greece

Local Institution - 425

Afula, 1834111

Israel

Local Institution - 420

Haifa, 3109601

Israel

Local Institution - 422

Jerusalem, 91031

Israel

Local Institution - 424

Jerusalem, 91120

Israel

Local Institution - 421

Nahariya, 22100

Israel

Local Institution - 423

Petah Tikva, 49100

Israel

Local Institution - 478

Florence, Tuscany 50134

Italy

Local Institution - 471

Florence, Tuscany 50139

Italy

Local Institution - 470

Allessandria, 15100

Italy

Local Institution - 464

Bologna, 40138

Italy

Local Institution - 466

Brindisi, 72100

Italy

Local Institution - 477

Cagliari, 09121

Italy

Local Institution - 462

Ferrara, 44124

Italy

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

Genoa, 16128

Italy

Local Institution - 473

Lecce, 73100

Italy

Maggiore Polyclinic Hospital, IRCCS Ca' Granda

Milan, 20122

Italy

Local Institution - 479

Modena, 41124

Italy

AORN A Cardarelli

Naples, 80131

Italy

AOU dell'Universita degli Studi della Campania Luigi Vanvitelli

Naples, 80131

Italy

Azienda Ospedaliero Universitaria S. Luigi Gonzaga

Orbassano, 10043

Italy

Local Institution - 469

Pavia, 27100

Italy

Local Institution - 468

Reggio Calabria, 89124

Italy

Local Institution - 465

Roma, 133

Italy

Local Institution - 474

Rozzano, 20089

Italy

Local Institution - 472

Varese, 21100

Italy

Local Institution - 463

Verona, 37134

Italy

Local Institution - 610

Nagoya, Aichi-ken 460-0001

Japan

Local Institution - 601

Kamogawa, Chiba 296-0041

Japan

Matsuyama Red Cross Hospital

Matsuyama, Ehime 790-8524

Japan

Ogaki Municipal Hospital

Ōgaki, Gifu 503-8502

Japan

Japanese Red Cross Society Himeji Hospital

Himeji, Hyōgo 6708540

Japan

Local Institution - 605

Hitachi, Ibaraki 317-0077

Japan

Local Institution - 603

Sagamihara, Kanagawa 252-0329

Japan

Local Institution - 0979

Sendai, Miyagi 980-8574

Japan

Local Institution - 607

Sendai, Miyagi 980-8574

Japan

Local Institution - 611

Nagasaki, Nagasaki 8528511

Japan

Local Institution - 604

Sakai, Osaka 5900197

Japan

Local Institution - 602

Shibuya City, Tokyo 150-8935

Japan

NTT Medical Center Tokyo

Shinagawa City, Tokyo 141-8625

Japan

Local Institution - 612

Chiba, 260-0852

Japan

Shonan Kamakura General Hospital

Kamakura, 247-8533

Japan

Local Institution - 609

Osaka, 545-8586

Japan

Chronic Care Center

Hazmiyeh, 00961

Lebanon

Local Institution - 545

Johor Bahru, Johor 80100

Malaysia

Hospital Sultanah Bahiyah

Alor Star, Kedah 05460

Malaysia

Local Institution - 544

Kuala Lumpur, Kuala Lumpur 59100

Malaysia

Hospital Raja Permaisuri Bainun

Ipoh, Perak 30990

Malaysia

Queen Elizabeth Hospital

Kota Kinabalu, Sabah 88586

Malaysia

Hospital Umum Sarawak

Kuching, Sarawak 93586

Malaysia

Local Institution - 580

Amsterdam, 1081 HV

Netherlands

Local Institution - 681

Barakaldo, 48903

Spain

Local Institution - 686

Barcelona, 08908

Spain

Local Institution - 685

Barcelona, 8035

Spain

Local Institution - 687

Madrid, 28028

Spain

Local Institution - 682

Oviedo, 33011

Spain

Local Institution - 684

Salamanca, 37007

Spain

Local Institution - 680

Seville, 41013

Spain

Local Institution - 683

Valencia, 46026

Spain

Local Institution - 720

Gothenburg, 413 45

Sweden

Local Institution - 722

Lund, SE-221 85

Sweden

Local Institution - 721

Stockholm, 141 86

Sweden

Local Institution - 760

Kaohsiung, San Ming Dist., 807

Taiwan

Local Institution - 762

Taichung, 40447

Taiwan

Local Institution - 761

Taipei, 100225

Taiwan

Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital

Bangkok, 10330

Thailand

Siriraj Hospital Mahidol University

Bangkok, 10700

Thailand

Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200

Thailand

University Hospital Farhat Hached

Sousse, 4031

Tunisia

Bone Marrow Transplant Center

Tunis, 1006

Tunisia

Aziza Othmana Hospital

Tunis, 1008

Tunisia

Military Hospital of Tunis

Tunis, 1008

Tunisia

Local Institution - 881

Adana, 01130

Turkey (Türkiye)

Local Institution - 885

Ankara, 06590

Turkey (Türkiye)

Local Institution - 882

Istanbul, 34093

Turkey (Türkiye)

Local Institution - 884

Istanbul, 34098

Turkey (Türkiye)

Local Institution - 880

Izmir, 35100

Turkey (Türkiye)

Local Institution - 883

Mersin, 33343

Turkey (Türkiye)

Local Institution - 925

Aberdeen, AB25 2ZN

United Kingdom

Local Institution - 921

Leeds, LS9 7TF

United Kingdom

Local Institution - 923

London, E1 1BB

United Kingdom

Whittington Hospital

London, N19 5NF

United Kingdom

University College London Hospitals NHS Foundation Trust - University College Hospital

London, NW1 2BU

United Kingdom

Local Institution - 928

London, SE1 9RT

United Kingdom

Local Institution - 924

London, SE5 9RS

United Kingdom

Local Institution - 929

Oxford, OX3 7LE

United Kingdom

Local Institution - 926

Sutton in Ashfield, NG17 4JL

United Kingdom