Prior participation on a clinical trial of luspatercept (ACE-536) in protocols eligible for participation in this study ACE-536-LTFU-001 with the following medical conditions: - myelodysplastic syndrome (MDS) - beta (ß)-thalassemia (THAL) - myelofibrosis (MF) MedDRA version: 20.0 Level: LLT Classification code 10074356 Term: Non-transfusion dependent thalassemia System Organ Class: 100000004850 MedDRA version: 20.0 Level: LLT Classification code 10068361 Term: MDS System Organ Class: 10029104
Conditions
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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: 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 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 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. 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. * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 223 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjec
Exclusion criteria
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. 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. 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. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term safety (including progression to acute myeloid leukemia (AML) and/or other malignancies/pre-malignancies) of luspatercept in subjects who have participated in other luspatercept clinical trials.;Secondary Objective: To follow subjects for overall survival. To evaluate treatment-emergent extramedullary hematopoiesis (EMH) masses.;Primary end point(s): 1) Adverse events (AEs) - Type, frequency, severity of AEs, relationship of treatment emergent adverse events to luspatercept. 2) Progression to high/very high risk myelodysplastic syndrome (MDS) or Progression to acute myeloid leukemia (AML) (MDS and myelofibrosis [MF] only) - Number and percentage of subjects progressing to high/very high risk MDS or AML. 3) Development of other malignancies/pre-malignancies - Number and percentage of subjects developing other malignancies/premalignancies.;Timepoint(s) of evaluation of this end point: 1) Adverse events (AEs) - Timeframe: Enrollment to 42 days post last dose 2) Progression to high/very high risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (MDS and myelofibrosis [MF] only) - Timeframe: Enrollment to Long-term Post-treatment Follow-up (LTPTFU) 3) Development of other malignancies/pre-malignancies - Timeframe: Enrollment to Long-term Post-treatment Follow-up (LTPTFU) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival - Time from date of randomization until death from any cause. Treatment-emergent EMH masses - Number and percentage of subjects developing treatment emergent EMH masses. ;Timepoint(s) of evaluation of this end point: Enrollment to Long-term Post-treatment Follow-up (LTPTFU) | — |
Countries
Australia, Belgium, Bulgaria, Canada, France, Germany, Greece, Israel, Italy, Lebanon, Malaysia, Netherlands, Spain, Sweden, Taiwan, Thailand, Tunisia, Turkey, United Kingdom, United States
Contacts
Public ContactGSM-CT
Bristol-Myers Squibb International Corporation
Outcome results
None listed