This study has been transitioned to CTIS with ID 2023-510009-16-00 check the CTIS register for the current data. Primary Objectives:• Phase 1 Only: To determine the recommended Phase 2 dose(RP2D) of quizartinib, in combination with chemotherapy,…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoints:
Safety:
* The safety profile of quizartinib administered in combination with reinduction
chemotherapy for up to 2 cycles, with optional consolidation
chemotherapy, and as a single-agent maintenance therapy over <=12 cycles.
* Phase 1 only: Number of DLTs in dose cohorts in Re-Induction Cycle 1.
Efficacy (i.e., the primary outcome measure):
* CRc rate after completion of up to 2 Re-Induction Cycles.
Pharmacokinetic:
* Estimates of AUC, apparent clearance (CL/F), and apparent volume of
distribution (Vd) for quizartinib and AC886 by the use of
PopPK modeling or other applicable methods.
Secondary outcome
Secondary Endpoints for Phases 1 and 2:
Efficacy (i.e., the secondary outcome measures):
* Duration of CR.
* Duration of CRc (i.e., from first documented CRc until documented
relapse).
* CR rate after completion of Re-Induction Cycle 1.
* CR rate after completion of up to 2 Re-Induction Cycles.
* CRc rate after completion of Re-Induction Cycle 1.
* Time to relapse, the rate of relapse after 1, 2 and 3 years, and the
cumulative incidence of relapse at the end of the study.
* OS, defined as the time from the start of Re-Induction
therapy until death from any cause.
* EFS defined as the time from the start of Re-Induction
therapy until the earliest date of the following:
* Refractory disease (or treatment failure) at the end of Re-Induction.
* Relapse after CR or CRi.
Death from any cause at any time during the study.
* Number of subjects proceeding to high-dose conditioning therapy/HSCT
(including transplant-related mortality).
Pharmacodynamic:
* Inhibition of FLT3-ITD and FLT3-wild-type autophosphorylation
activity in an ex-vivo PIA during Re-Induction, Maintenance, and at the
time of relapse.
* FLT3-ITD to FLT3-wild-type allelic ratio at Screening, during Re-
Induction, and at the time of relapse.
* Mutations present in blasts (e.g., in the kinase and juxtamembrane
domains of FLT3-ITD and other mutations known to be associated with
AML) at Screening and at the time of refractory disease or relapse.
Biomarker:
* MRD for subjects who are in CR or CRi at Screening, end of Re-
Induction Cycle 1, end of Re-Induction Cycle 2, and at the time of
relapse by next generation sequencing.
Others:
* Acceptability including palatability of quizartinib formulations.
Exploratory Endpoints:
* The relationship between quizartinib and AC886 exposure and clinical
response.
Background summary
The main purpose of this study is to gather information about an
investigational drug, called quizartinib that may help to treat your disease.
An investigational drug is a medication that is still being studied and has not
yet been approved for use in your country (by the European Medicine Agency
(EMA) in Europe) Quizartinib was designed to work against cancer cells that
have FLT3-ITD. It is currently being tested in other studies to see if it works
in adults with this type of AML.
This study has been granted approval by an Institutional Review Board/Ethics
Committee, an independent group of experts who ensure your rights, safety and
well-being are protected. Children and young adults from 1 month old up to 21
years old may be part of this study. We expect that about 52 patients with AML
may take part in this research study, which is being conducted at approximately
35 study sites around the world (in the United States and Europe).
You may not participate in this study if:
• you are an employee of the study site;
• You are an immediate family member of an employee of the study staff. An
immediate family member means a spouse, parent, child or sibling. Family
members can be biological or legally adopted, or
• You are an employee of Daiichi Sankyo, Inc., the sponsor of this study.
There may be other reasons that you are not able to participate. The Study
Doctor will discuss these reasons with you.
Throughout the rest of this consent form, Daiichi Sankyo, Inc. will be referred
to as the *Sponsor*. Daiichi Sankyo, Inc. is a pharmaceutical (drug) company
and is responsible for organizing and funding this study including paying your
research team to perform the study.
Your study doctor and research team will ask you many questions about your
current and past health. Please be honest in answering these questions
(including past and present medications), or else it may not be safe for you to
be in this study. If you agree to take part in this study, you must first read
and sign this consent form. You will get a signed copy of this consent form for
your records.
Study objective
This study has been transitioned to CTIS with ID 2023-510009-16-00 check the CTIS register for the current data.
Primary Objectives:
• Phase 1 Only: To determine the recommended Phase 2 dose
(RP2D) of quizartinib, in combination with chemotherapy, for
subjects in the older (>=1 year old to <=21 years old) and younger
(>=1 month old to <12 months old) age groups.
• To determine the composite complete remission (CRc) rate (i.e.,
complete remission [CR] + CR with incomplete recovery [CRi])
after completion of up to 2 Re-Induction Cycles.
• To determine the safety and cumulative toxicity of quizartinib
administered in combination with re-induction therapy for up to 2
cycles, with optional consolidation chemotherapy, and as a single-agent
maintenance therapy over <=12 cycles.
• To determine estimates of individual PK parameters of quizartinib
and AC886 (metabolite of quizartinib).
Secondary Objectives:
• To determine the CR rate after completion of up to 2 Re-Induction
Cycles.
• To determine the durations of CRc and CR.
• To assess the time to relapse, the rate of relapse after 1, 2 and 3
years, and the cumulative incidence of relapse at the end of study (when the
last subject enrolled has had 3 years of follow-up from
the date of enrollment).
• To determine the rates of CR and CRc after completion of Re-
Induction Cycle 1.
• To assess overall survival (OS) and event-free survival (EFS) at 1,
2, and 3 years.
• To assess the number of subjects proceeding to high-dose
conditioning therapy/ hematopoietic stem cell transplantation
(HSCT).
• To assess the activity of quizartinib on FLT3-ITD and FLT3-wildtype
autophosphorylation activity by an ex-vivo plasma inhibitory
activity assay (PIA) during Re-Induction, Maintenance, and at the
time of relapse.
• To assess the FLT3-ITD/FLT3-wild-type allelic ratio at Screening,
during Re-Induction, and at the time of relapse.
• To evaluate somatic mutations present in blasts (e.g., in the kinase and
juxtamembrane domains of FLT3-ITD and other mutations known
to be associated with AML) at Screening and at the time of
refractory disease or relapse.
• To assess rate of CRc (CR, CrRi) without minimal residual disease (MRD) using
next generation sequencing
• To assess the acceptability including palatability of quizartinib
formulations.
Exploratory Objectives:
• To explore the relationship between quizartinib (and AC886)
exposure and clinical response
Study design
This is a global open-label, multi-center, single arm, Phase 1/2 study to
evaluate the
safety, PK, PD, and efficacy of quizartinib administered in combination with
fludarabine / cytarabine (FLA) + liposomal daunorubicin (DNX) (Re-Induction
Cycle 1) and FLA (Re-Induction Cycle 2) chemotherapy for re-induction, with
optional consolidation chemotherapy, and as a single agent maintenance
therapy (after optional, but strongly encouraged, HSCT per standard of care),
in pediatric subjects with R/R FLT3-ITD (+) AML aged >=1 month old to <18 years
old (and young adults up to 21 years old) with FLT3-ITD mutations.
Dose-Escalation/De-escalation and Dose-Expansion:
Phase 1 (Dose Escalation/De-escalation):
In Phase 1, cohorts of up to 9 subjects per dose-level will be enrolled to
determine the recommended Phase 2 dose (RP2D) of quizartinib in the older
age group first. In Re-Induction Cycle 1, subjects will be administered the FLA
+ DNX regimen on Days 1 to 5, followed by quizartinib on Days 6 to 28.
Dose-limiting toxicities (DLTs) will be assessed during Re-Induction Cycle 1.
In Re-Induction Cycle 2, subjects will be administered the FLA regimen on
Days 1 to 5, followed by quizartinib on Days 6 to 28.
Following Re-Induction, subjects should be thoroughly evaluated for eligibility
to undergo allogeneic HSCT according to standard of care. Subjects may
receive optional consolidation therapy if an allogeneic HSCT is not available
immediately. Subjects in remission after HSCT and subjects who do not
undergo HSCT, but who achieve at least a partial remission (PR) or morphologie
leukemia-free state (MLFS) after Re-
Induction, will be treated with up to 12 continuous 28-day cycles of quizartinib
maintenance therapy.
The safety and PK data for the older age group will be used, along with
population PK (PopPK) modeling (if available) to determine the RP2D for the
older group and the starting dose of quizartinib for the younger age group.
Once the recommended Phase 1 starting dose for the younger age group has
been determined from the data collected in the older age group, the younger
age group will be enrolled using a Rolling 6 dose escalation/de-escalation
design to determine the RP2D for younger subjects.
In the older age group, PK data is required from at least 9 subjects for a dose
to
be considered as the RP2D. Additional PK data will be collected in Phase 2 to
confirm the validity of the model established in Phase 1.
Older Age Group (>=1 Year Old to <=21 Years Old):
In the older age group, up to 9 subjects will be enrolled at Dose Level 1:
40 mg/m2 once daily for a BSA <1.5 m2 and a flat dose of 60 mg once daily for
a BSA >=1.5 m2. Enrollment will be suspended once 9 subjects have been
enrolled or >= 3 DLTs have been observed. Additional dose cohorts may be
enrolled based on the observed DLTs and the PK data collected for the first
cohort, as indicated in the dose escalation/de-escalation design. Following
completion of enrollment for subjects at Dose Level 1, the doses of quizartinib
to be used at other Dose Levels will be determined based upon a review of the
available PK data. A PopPK model will also be used, if available. Once the
RP2D has been determined for the older age group, enrollment in the Phase 2
dose-expansion portion of the study will be initiated for this age group. The
Phase 2 expansion cohort can enroll the older age group before the Phase 1
dose escalation/de-escalation study has been completed in the younger age
group.
Younger Age Group (>=1 Month Old to <12 Months Old):
Three subjects in the younger age group will be enrolled and treated at the
quizartinib starting dose determined after the full data review has been
completed for the older age group. Additional subjects and dose cohorts may
be enrolled, as indicated in the Rolling 6 dose escalation/de-escalation design.
Once the RP2D has been determined for the younger age group, enrollment in
the Phase 2 dose-expansion portion of the study will be initiated for this age
group. However, recognizing the difficulties in enrolling in this younger age
group, the study may be closed by the sponsor prior to completing enrollment
in this age group.
Phase 2 (Dose-Expansion):
Subjects enrolled in Phase 2 will receive the RP2D of quizartinib for their
respective age group, administered in combination with FLA + DNX (ReInduction
Cycle 1) and FLA (Re-Induction Cycle 2) chemotherapies for Re-
Induction.
Following Re-Induction, subjects should be thoroughly evaluated for eligibility
to undergo allogeneic HSCT. Subjects may receive optional consolidation
therapy if an allogeneic HSCT is not available immediately. Subjects in
remission after HSCT and subjects who are not eligible for HSCT, but who
achieve at least (PR) or MLFS after Re-Induction will be treated with
up to 12 continuous 28-day cycles of quizartinib maintenance therapy, given at
the same dose as used during Re-Induction.
Study Treatment:
Re-Induction (2 Cycles):
Re-Induction Cycle 1 (FLA + DNX + Quizartinib)
Subjects will be administered the following medications during Re-Induction
Cycle 1:
• Intrathecal (IT) triple chemotherapy prophylaxis may be given within 1
week prior to beginning Re-Induction Cycle 1. It is recommended that
IT prophylaxis be administered at least 24 hours prior to the start of Re-
Induction Cycle 1, Day 1 chemotherapy. Cycle 1, Day 1 is defined as
the start date of the fludarabine, cytarabine, and daunorubicin
chemotherapy (not IT chemotherapy).
Investigators will administer IT cytarabine, methotrexate, and either
prednisolone or hydrocortisone. Doses will be based on the subject*s
age and standard practice at each site.
Additional IT chemotherapy may be administered at the investigator*s discretion
for subjects with central nervous system (CNS)2 disease during Re-Induction.
For CNS3 disease, IT chemotherapy will be administered until the cerebrospinal
fluid (CSF) is clear of blasts, then 1 additional dose of IT chemotherapy will
be administered
• Fludarabine: 30 mg/m2/ day IV infusion given over 30 minutes on Days
1 through 5.
• Cytarabine: 2000 mg/m2/day IV infusion given over 3 hours on Days 1
through 5 (begin 4 hours after the start of fludarabine).
• Liposomal daunorubicin: 60 mg/m2/day IV infusion given over 120
minutes on Days 1, 3 and 5 (administer after fludarabine).
• Quizartinib: orally once daily starting on Day 6 and continuing through
Day 28. If quizartinib is interrupted, missed doses will not be made up.
* Phase 1: dose will be assigned at study entry.
* Phase 2: subjects will be treated at the RP2D.
• IT triple chemotherapy prophylaxis will also be given after Re-Induction
Cycle 1 Day 28, but before the start of Re-Induction Cycle 2.
Investigators will administer IT cytarabine, methotrexate, and either
prednisolone or hydrocortisone. Doses will be based on the subject*s
age and standard practice at each site.
Additional IT chemotherapy may be administered at the Investigator*s
discretion for subjects with CNS2 disease during Re-Induction. For CNS3
disease, IT chemotherapy will be administered until the CSF is clear of
blasts,then 1 additional dose of IT chemotherapy will be administered.
A bone marrow aspirate will be collected upon blood count recovery or on Day
29 (±1 Day), whichever occurs first. If the marrow is hypoplastic or if
response cannot be determined, then collect weekly complete blood counts
with differentials (CBC) until count recovery or Day 56, whichever occurs
first. A repeat marrow aspirate should be obtained upon count recovery up to
Day 56. If counts have not recovered by Day 56, perform the repeat marrow
aspiration and collect a CBC on Day 56 (±3 Days).
Re-Induction Cycle 2 (FLA + Quizartinib):
At the Investigator*s discretion, to allow for blood counts to recover or other
reasons, the second Re-Induction cycle may start up to 70 days after Day 1 of
the first Re-Induction cycle. Subjects are eligible to receive Re-Induction
Cycle
Intervention
NA
Study burden and risks
A: Medicine or other interactions
There are risks associated with taking part in any research study. One risk is
that subject may get a drug or dose of a drug that does not help treat his
disease, or that makes his condition worse. Another risk is that the drugs can
cause side effects which may be mild and reversible but that can be very
severe, long lasting and life threatening. Side effects can even cause death.
Subject will be watched carefully for side effects. For investigational drugs,
including quizartinib, there may be side effects that we do not know about at
this time. During the study, subject will be told about newly discovered side
effects or important findings which may affect his health or his willingness to
stay on the study. Subject may be asked to read and sign a new Informed Consent
Form that shows that Subject have been given new information relating to this
study.
Since many drugs used to treat leukemia make fast-growing cancer cells slow
down or die, they can also make fast-growing normal cells slow down or die.
This includes the blood cells that help fight infection (white blood cells),
the blood cells that help blood clot (platelets), and the blood cells that
carry oxygen (red blood cells). While subject is taking part in this study, his
blood cell counts will be checked closely, and subject may need blood and/or
platelet transfusions if subject have anemia (not have enough red blood cells)
or have a low platelet count or are bleeding.
Subject need to tell the study doctor or a study staff immediately if subject
have any side effects. In particular, watch for any of the following:
• A fever of 38.1°C or above. This could be a sign of an infection. If subject
have a low white blood cell count, an infection with fever could be serious,
life threatening or fatal. subject may have to take drugs to fight infections
and/or go into the hospital.
• Any kind of infection.
• Tiredness or shortness of breath. This could be a sign of anemia. If anemia
gets severe, subject may need a red blood cell transfusion.
• If subject bruise or bleed easily or do not stop bleeding when you get hurt.
This could be a sign that his platelet count is low. A low platelet count could
be serious or life threatening. subject may need a platelet transfusion.
• Any kind of irregular heartbeat, heart pounding, fainting or blackouts. This
could be a sign that the study treatment, and/or other medications, could be
interfering with the way your heart works.
• Any rashes or skin ulcers. These can have severe complications, so the doctor
may need to treat these right away.
If subject have side effects, the doctor may also choose to stop the study
treatments until he get better, lower the dose of quizartinib or permanently
stop the study treatments.
B: Side effects of the study medicinal product
Find detailed information in Appendix D of the informed consent..
C: Contraception, pregnancy and breast-feeding
The drugs used in this study may affect an unborn baby or a breastfeeding
infant. If subject are pregnant or become pregnant, the study medication may
cause birth defects or death to the unborn baby. Breast-feeding could expose
the baby to study medication. If you are a pregnant woman, nursing or intend to
nurse the baby, subject cannot take part in this study.
Find detailed information in Appendix D of the informed consent.
D: Risks associated with the evaluation procedures specific to the study
Find detailed information in Appendix D of the informed consent..
211 MT. AIRY ROAD 211 MT. AIRY ROAD
Basking Ridge NJ 07920-2311
US
211 MT. AIRY ROAD 211 MT. AIRY ROAD
Basking Ridge NJ 07920-2311
US
Listed location countries
Age
Inclusion criteria
1. Diagnosis of AML according to the World Health Organization (WHO) 2008
classification with >=5% blasts in bone marrow, with or without extramedullary
disease.
2. Subjects must be in first relapse or refractory to first-line high-dose
chemotherapy with no more than 1 attempt (1 to 2 cycles of induction
chemotherapy) at remission induction. Prior HSCT is permitted.
3. Presence of the FLT3-ITD activating mutation in bone marrow or peripheral
blood that is confirmed by central testing. The results of FLT3 ITD testing
must be obtained prior to the first dose of quizartinib (Re-Induction Cycle 1,
Day 6). Subjects may be enrolled and begin treatment with the systemic
protocol therapy pending the result of the FLT3 ITD testing; however, subjects
with a negative central and local FLT3 ITD test who are enrolled and have begun
systemic protocol treatment will be discontinued from the study. Subjects may
also be enrolled and begin treatment based upon the results of a local FLT3-ITD
laboratory test (performed on or after the date of diagnosis of R/R disease);
however, a sample must be sent to the central laboratory for confirmation.
Subjects with a negative central FLT3-ITD test who are enrolled and have begun
treatment based upon results of a FLT3-ITD test conducted at a local laboratory
may continue on the study at the investigator*s discretion after discussion
with the medical monitor.
4. Subjects must be between 1 month and <=21 years of age at the time the ICF is
signed.
5. Karnofsky performance status score of >50% for subjects >16 years of age,
and a Lansky performance status score of >50% for subjects <=16 years of age.
6. Subjects must have fully recovered from the acute clinically significant
toxicity effects of all prior chemotherapy, immunotherapy, or radiotherapy
prior to Re-Induction Cycle 1, Day 1:
a. Myelosuppressive chemotherapy:
* For subjects who relapse while they are receiving cytotoxic
therapy, at least 21 days must have elapsed since the completion of cytotoxic
therapy.
* Cytoreduction with hydroxyurea can be initiated and
continued for up to 1 day prior to the start of systemic protocol therapy.
Subjects may also receive
low dose cytarabine (100 mg/m2/dose once daily for up to 5 days) for
cytoreduction and completed up to 1 day prior to the start of systemic protocol
therapy.
* Subjects who have received other FLT3 inhibitors (eg,
lestaurtinib, sorafenib), with the exception of quizartinib, are eligible for
this study.
b. Hematopoietic growth factors: At least 3 days since the completion of
therapy with a growth factor.
c. Biologic (anti-neoplastic agent): At least 7 days since the completion
of therapy with a biologic agent. However, for agents that have known adverse
events
(AEs) occurring beyond 7 days after administration, this period must be
extended beyond the time during which AEs are known to occur. The duration of
this
interval must be discussed with the medical monitor.
d. >=14 days for local external radiation therapy (XRT) for CNS chloromas.
e. >=90 days must have elapsed if prior total body radiation (TBI) or
craniospinal XRT occurred.
f. At least 90 days must have elapsed since HSCT. For subjects with a
history of graft versus host disease (GVHD), immunosuppressive therapy must be
stable for
>=2 weeks in subjects with a history of <= Grade 2 GVHD and for >=4 weeks in
subjects with a history of Grade 3/4 GVHD.
g. Investigational drug/device: at least 30 days or 5 half-lives since the
completion of therapy, whichever is longer.
7. Adequate renal and hepatic functions as indicated by the following
laboratory values:
a. Serum creatinine concentration <=1.5 × institutional upper limit of
normal (ULN) based on the age and sex, or creatinine clearance (CrCl) >0.84
mL/s (as
measured preferably by a nuclear glomerular filtration rate scan, timed
urine collection for CrCl, or calculated by the Schwartz formula [for subjects
<18 years] or
Cockcroft-Gault [for subjects >=18 years] and normalized to a BSA of 1.73m2).
b. Total bilirubin <1.5 × ULN for age or normal conjugated bilirubin (<5 ×
ULN if related to leukemic involvement).
c. Alanine aminotransferase (ALT) <5 × ULN (<10 × ULN if related to
leukemic involvement).
8. Left Ventricular (LV) fractional shortening of >=29% by echocardiogram, OR a
left ventricular ejection fraction (LVEF) of >=50% by echocardiogram or
radionuclide angiogram.
9. Female subjects of childbearing potential must have a negative urine or
serum pregnancy test confirmed within 2 weeks prior to enrollment. Female
subjects of childbearing potential must be willing to use highly effective
birth control upon enrollment, during the treatment period, and for 6 months
following the last dose of quizartinib, etoposide, fludarabine, methotrexate or
cytarabine, whichever is later. Female subjects are considered of childbearing
potential following menarche, unless permanently sterile (undergone a
hysterectomy, bilateral salpingectomy or bilateral oophorectomy). Female
subjects must not donate or retrieve for their own use ova from the time of
Screening and throughout the treatment period, and for at least 6 months
following the last dose of quizartinib, etoposide, fludarabine, methotrexate,
or cytarabine, whichever is later.
10. Female subjects with infants must agree not to breastfeed their infants
while on this study.
11. Male subjects must be surgically sterile or willing to use highly effective
birth control during the treatment period, and for 6 months following the last
dose of quizartinib, etoposide, fludarabine, methotrexate, or cytarabine,
whichever is later. Male subjects must not freeze or donate sperm starting at
Screening and throughout the treatment period, and at least 6 months following
the last dose of quizartinib, etoposide, fludarabine, methotrexate or
cytarabine, whichever is later.
12. Subjects and/or their parents or legal guardians must be capable of
understanding the investigational nature, potential risks, and benefits of the
study. All subjects and/or their parents or legal guardians must sign a
written ICF prior to the start of any study-specific qualification procedures.
Age appropriate assent will be obtained per institutional guidelines.
Inclusion Criteria*Continuation:
Subjects must satisfy all of the following criteria to receive continuation
therapy:
1. Must have achieved at least a PR in Re-Induction or continue to be in
remission as defined by local practice standards after HSCT.
2. Subject's absolute neutrophil count (ANC) must be >=0.5 × 109/L and platelets
(PLTs) must be >=50 × 109/L at the time of initiating continuation therapy.
3. All Grade 3 and 4 toxicities have resolved to Grade 2 or less.
4. Able to begin Continuation Phase within 70 days of the previous Re-Induction
Cycle Day 1 (for those who do not undergo HSCT) or 30*180 days after allogeneic
HSCT.
5. For subjects with a history of GVHD, immunosuppressive therapy must be
stable for >=2 weeks in subjects with a history of <= Grade 2 GVHD and for >=4
weeks in subjects with a history of Grade 3/4 GVHD.
Exclusion criteria
Subjects who meet any of the following criteria will be disqualified from
entering the study:
1. Diagnosis of isolated CNS relapse (CNS2/3 disease is allowed if treated with
additional IT chemotherapy).
2. Diagnosis of acute promyelocytic leukemia (APL), juvenile myelomonocytic
leukemia (JMML), French-American-British (FAB) classification M3 or WHO
classification of APL with translocation, t(15;17)(q22;q12), or myeloid
proliferations related to Down syndrome.
3. Uncontrolled or significant cardiovascular disease, including:
a. Diagnosed or suspected congenital long QT syndrome.
b. History of clinically significant ventricular arrhythmias (such as
ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes
[TdP]); any history of arrhythmia will be
discussed with the medical monitor prior to subject*s entry into the study.
c. QT interval corrected >450 ms:
* QTc interval corrected with Bazett*s formula (QTcB) for subjects < 6
years of age at the time of enrollment.
* QTc interval corrected with Fridericia*s formula (QTcF) for subjects
>= 6 years of age at the time of enrollment.
d. History of uncontrolled angina pectoris or myocardial infarction within
6 months.
e. History of second (Mobitz II) or third degree heart block (subjects
with pacemakers are eligible if they have no history of fainting or clinically
relevant arrhythmias while
using the pacemaker).
f. Heart rate <50 beats/minute on screeening electrocardiogram (ECG).
g. Uncontrolled hypertension (i.e., systolic blood pressure and /or
diastolic blood pressure that is, on repeated measurement, at or above the 95th
percentile for sex, age,
and height).
h. History of complete left bundle branch block.
i. History of New York Heart Association Class 3 or 4 heart failure.
4. Subjects will be excluded if they have a systemic fungal, bacterial, viral
or other infection that is exhibiting ongoing signs/symptoms related to the
infection without improvement despite appropriate antibiotics or other
treatment. The subject needs to be off vasopressors and have negative blood
cultures for at least 48 hours prior to the start of systemic protocol therapy..
5. Known active clinically relevant liver disease (e.g., active hepatitis B or
active hepatitis C).
6. Known history of human immunodeficiency virus (HIV).
7. History of hypersensitivity to any of the study medications or their
excipients.
8. Subject is receiving or is anticipated to receive concomitant chemotherapy,
radiation, or immunotherapy other than as specified in the protocol.
9. Any significant concurrent disease, illness, psychiatric disorder or social
issue that would compromise subject safety or compliance, interfere with
consent/assent, study participation, follow up, or interpretation of study
results.
10. Currently participating in other investigational interventional procedures
(does not include observational procedures or long-term follow-up for previous
interventional studies).
11. Otherwise considered inappropriate for the study by the Investigator
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 |
|---|---|
| EU-CTR | CTIS2023-510009-16-00 |
| EudraCT | EUCTR2016-002919-18-NL |
| CCMO | NL65309.078.18 |