This study has been transitioned to CTIS with ID 2022-502498-40-00 check the CTIS register for the current data. Primary Objective: To evaluate the long-term safety (including progression to acute myeloid leukemia (AML) and/or other malignancies/pre…
ID
Source
Brief title
Condition
- Anaemias nonhaemolytic and marrow depression
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1- Adverse events (AEs): Type, frequency, severity of AEs, relationship of
treatment emergent adverse events to luspatercept. Timeframe: Enrollment to 42
days post last dose.
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
. Timeframe; Enrollment to LTPTFU
3- Development of other malignancies/pre-malignancies. Number and percentage
of subjects developing other malignancies/premalignancies. Timeframe;
Enrollment to LTPTFU
Secondary outcome
Overall survival: Time from date of randomization until death from any cause.
Timeframe: Enrollment to LTPTFU
Treatment-emergent EMH masses - Number and percentage of subjects developing
treatment emergent EMH masses
Background summary
This is a Phase 3b, open-label, single-arm, rollover study intended to evaluate
the long-term safety of luspatercept in subjects who have participated in other
luspatercept clinical trials. The purpose of the study is to ensure continued
supply of luspatercept for subjects who continue to benefit from luspatercept
treatment at the time the parent protocol is closed and luspatercept is not
commercially available and reimbursable in the participating country for the
indication that subject is being treated. This study will also include subjects
previously on placebo arm from parent protocols (at the time of unblinding or
in follow-up) crossing over to luspatercept treatment (provided subjects have
met all requirements for entering the rollover study as per the respective
parent protocols).
This study is designed to provide continued safety monitoring of subjects
already receiving clinical benefit in the opinion of the investigator from
luspatercept treatment in the parent study protocol. In this study, subjects
will continue treatment with luspatercept at the same dose level and schedule
of the last visit of the parent luspatercept clinical study. For placebo arm
subjects from parent protocols (at the time of unblinding or in follow-up)
crossing over to luspatercept treatment (provided subjects have met all
requirements for entering the rollover study as per the parent protocol), the
starting dose level is 1.0 mg/kg Q3W. Treatment will continue until progression
of disease, benefit no longer being received as deemed by the investigator,
and/or upon commercial availability and/or reimbursement of luspatercept for
the indication in the participating country.
In addition, this study will provide an opportunity to those subjects who are
currently in Post-treatment Follow-up Phase of the parent protocol to continue
to be followed until the Long-term Post-treatment Follow-up (LTPTFU)
commitments have been met.
Study objective
This study has been transitioned to CTIS with ID 2022-502498-40-00 check the CTIS register for the current data.
Primary 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 Objectives:
- To follow subjects for overall survival.
- To evaluate treatment-emergent extramedullary hematopoiesis (EMH)
masses.
Exploratory Objectives: IPSS-R progression from very low at baseline to low or
intermediate risk; low at baseline to intermediate-risk myelodysplastic
syndrome (in MDS subjects only)
Study design
This Phase 3b open-label, single-arm, rollover study is intended to evaluate
the long-term safety of luspatercept and to provide treatment with luspatercept
to the following subjects:
• Subjects 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 in the opinion of the investigator from continuing treatment
with luspatercept.
• Placebo arm subjects from parent protocol (at the time of unblinding or in
follow-up) crossing over to luspatercept treatment (provided subjects have met
all requirements for entering the rollover study as per the parent protocol).
Patients who were assigned to the placebo arm of the parent protocol (who have
no parent protocol provision to cross over to luspatercept treatment) cannot
receive luspatercept through this protocol.
• Subjects 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
(provided they meet requirements as per parent protocol to cross over to
luspatercept treatment).
Intervention
Subjects will receive luspatercept during the Treatment Phase of the study. The
dose and schedule of luspatercept in this study will be determined by the
luspatercept dose the subject is receiving at the time of transitioning from
the parent luspatercept study, taking into account the subject*s last dose and
schedule. For placebo arm subjects from parent protocol (at the time of
unblinding or in follow-up) crossing over to luspatercept treatment (provided
subjects have met all requirements for entering the rollover study as per the
parent protocol) the starting dose will be 1.0 mg/kg Q3W.
Study burden and risks
This is a Phase 3b, open-label, single-arm, rollover study intended to evaluate
the long-term safety of luspatercept in subjects who have participated in other
luspatercept clinical trials. The purpose of the study is to ensure continued
supply of luspatercept for subjects who continue to benefit from luspatercept
treatment at the time the parent protocol is closed and luspatercept is not
commercially available and reimbursable in the participating country for the
indication that subject is being treated. This study will also include subjects
previously on placebo arm from parent protocols (at the time of unblinding or
in follow-up) crossing over to luspatercept treatment (provided subjects have
met all requirements for entering the rollover study as per the respective
parent protocols).
This study is designed to provide continued safety monitoring of subjects
already receiving clinical benefit in the opinion of the investigator from
luspatercept treatment in the parent study protocol. In this study, subjects
will continue treatment with luspatercept at the same dose level and schedule
of the last visit of the parent luspatercept clinical study. For placebo arm
subjects from parent protocols (at the time of unblinding or in follow-up)
crossing over to luspatercept treatment (provided subjects have met all
requirements for entering the rollover study as per the parent protocol), the
starting dose level is 1.0 mg/kg Q3W. Treatment will continue until progression
of disease, benefit no longer being received as deemed by the investigator,
and/or upon commercial availability and/or reimbursement of luspatercept for
the indication in the participating country.
The burden for study subjects are limited to side effects of study drug, which
they may also have had during the parent protocol they participated and
visiting the study center during the treatment period. The study procedures
are limited compared to the parent protocol and majority of these procedures
are performed as part of standard care, if required.
The objective of the LTFU protocol is to evaluate the long-term safety during
use of Luspatercept (for the subjects still receiving benefit of the IP) and
after use of Luspatercept (for the discontinued subjects that had received the
IP). Endpoints are aligned with this intent, evaluating overall adverse events
and the development of other malignancies/pre- malignancies (note that
progression to high risk MDS and progression to AML mentioned in the primary
endpoint are described as part the SAE definition, hence to be mandatorily
informed in the study) as well as overall survival.
Other than IP management requiring blood draws there are no other perceived
inherent risks for the protocol with mandatorily collected datapoints intended
to be permissive for study drug application or descriptive regarding safety
complications (AE reporting), hence, aligned with the objective/endpoints
description.
Some procedures are performed under standard of care and although not protocol
mandated these are part of evaluation and management of the underlying disease.
These are described in the protocol and their respective risks are disclosed in
the ICF form.
Morris Avenue 86
Summit, New Jersey 07901
US
Morris Avenue 86
Summit, New Jersey 07901
US
Listed location countries
Age
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 cross-over 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).
Exclusion criteria
1. 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- 536LTFU-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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2018-002915-93 |
| EU-CTR | CTIS2022-502498-40-00 |
| EudraCT | EUCTR2018-002915-93-NL |
| CCMO | NL69072.029.19 |