JOURNAL ONKOLOGIE – STUDIE

LUSPLUS

Assessment of Effectiveness and Safety of Luspatercept in Patients Suffering From Lower-risk Myelodysplastic Syndrome.

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05181592

Studienbeginn:
Oktober 2021

Letztes Update:
12.10.2023

Wirkstoff:
Luspatercept

Indikation (Clinical Trials):
Preleukemia, Myelodysplastic Syndromes, Syndrome

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
GWT-TUD GmbH

Collaborator:
Celgene

Studienleiter

Katharina Götze, Prof.
Principal Investigator
Klinikum rechts der Isar der Technischen Universität München

Kontakt

Arnold Schröder, Dr.
Kontakt:
Phone: +4935125933
Phone (ext.): 241
E-Mail: lusplus@g-wt.de» Kontaktdaten anzeigen

Studienlocations
(3 von 17)

OncoResearch Lerchenfeld GmbH
22081 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps

Onkologische Schwerpunktpraxis Heidelberg
69115 Heidelberg
(Baden-Württemberg)
GermanyZurückgezogen» Google-Maps

Gynäkologisches Tumorzentrum am Universitätsklinikum Leipzig
4103 Leipzig
DeutschlandRekrutierend» Google-Maps

Gemeinschaftspraxis Hämatologie/Onkologie Magdeburg
39104 Magdeburg
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps

Pankreaskrebszentrum am Klinikum rechts der Isar
Ismaninger Straße 22
81675 München
DeutschlandRekrutierend» Google-Maps

Praxis für Hämatologie und Onkologie
46145 Oberhausen
(Nordrhein-Westfalen)
GermanyZurückgezogen» Google-Maps

Medizinische Universität Innsbruck
6020 Innsbruck
AustriaRekrutierend» Google-Maps

Medizinische Universität Wien
1090 Vienna
AustriaRekrutierend» Google-Maps

Institut Català d' Oncologia de Badalona
8916 Badalona
SpainNoch nicht rekrutierend» Google-Maps

Hospital Vall d´Hebron
08023 Barcelona
SpainRekrutierend» Google-Maps

Hospital General Universitario Gregorio Marañón
28009 Madrid
SpainRekrutierend» Google-Maps

Hospital Universitario Central de Asturias
33011 Oviedo
SpainRekrutierend» Google-Maps

University Hospital of Salamanca
37007 Salamanca
SpainRekrutierend» Google-Maps

Hospital Universitario y Politecnico La Fe de Valencia
46026 Valencia
SpainRekrutierend» Google-Maps

Universitätsspital Basel
4031 Basel
SwitzerlandRekrutierend» Google-Maps

Clinica di Ematologia Istituto oncologico della Svizzera Italiana
6500 Bellinzona
SwitzerlandRekrutierend» Google-Maps

Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor
3010 Bern
SwitzerlandRekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

Detailed Description:

This is a phase IIIb, single arm, multicenter study to further explore the efficacy and

safety of luspatercept in subjects with anemia due to IPSS-R very low-, low-, or

intermediate-risk MDS with RS who require RBC transfusions. The study will consist of a

screening period, a treatment period (primary phase and extension phase), and a posttreatment

follow-up period.

The study will involve study sites in Germany, France, Austria and Switzerland. It is planned

to include 70 patients to receive treatment with luspatercept to end up with 64 evaluable

subjects.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Subject is 18 years of age or older at the time of signing the informed consent form

(ICF)

2. Subject is able to understand and voluntarily sign the ICF prior to any study-related

assessments/procedures being conducted

3. Subject has documented diagnosis of MDS according to WHO classification that meets

IPSS-R classification[3] of very low-, low-, or intermediate-risk disease, and the

following:

- Ring sideroblasts (RS) ≥ 15% of erythroid precursors in bone marrow or ≥ 5% if

SF3B1 mutation is present

- Less than 5% blasts in bone marrow

- Peripheral blood white blood cell (WBC) count < 13,000/μL

4. Subject must be one of the following:

- Refractory to prior ESA treatment: Documentation of non-response or response that

was no longer maintained to prior ESA-containing regimen, either as a single

agent or in combination (e.g. with granulocyte colony-stimulating factor

[G-CSF]). The ESA regimen must be either:

- Recombinant human erythropoietin ≥ 40,000 IU/week for at least 8 weeks

(=doses) or equivalent; or

- Darbepoetin-α ≥ 500 μg q3w for at least 4 doses or equivalent

- Intolerant to prior ESA treatment: Documentation of discontinuation of prior ESA

containing regimen, either as a single agent or in combination (e.g. with G-CSF),

at any time after introduction due to intolerance or an adverse event (AE)

- ESA ineligible: Low chance of response to ESA based on endogenous serum

erythropoietin (EPO) level > 200 U/L for subjects not previously treated with

ESAs

- Refractory to- /relapsed after prior HMA treatment1: Treatment failure/relapse

after at least six (azacitidine) or four (decitabine) 4-week treatment cycles

except for del(5q) MDS

- Refractory to- /relapsed after prior lenalidomide treatment1 except for del(5q)

MDS

5. If previously treated with ESAs or G-CSF/granulocyte-macrophage colony-stimulating

factor (GM-CSF), both agents must be discontinued ≥ 4 weeks prior to the date of

starting treatment with the Investigational medicinal Product (IMP) in this study

6. Required RBC transfusions, as documented by the following criteria:

- Average transfusion requirement of ≥ 2 units/8 weeks of packed RBCs confirmed for

a minimum period of 16 weeks immediately preceding start of treatment with IMP

- Hemoglobin (Hb) levels at the time of or within 7 days prior to administration of

an RBC transfusion must be ≤ 10.0 g/dL in order for the transfusion to be counted

towards meeting eligibility criteria. RBC transfusions administered when Hb

levels are > 10 g/dL and/or RBC transfusions administered for elective surgery do

not qualify as a required transfusion for the purpose of meeting eligibility

criteria

- No consecutive 56-day period that is RBC transfusion-free during the 16 weeks

immediately prior to starting treatment with IMP

7. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2

8. A female of childbearing potential (FCBP) for this study is defined as a sexually

mature woman who: (1) has not undergone a hysterectomy or bilateral oophorectomy; or

(2) is not naturally postmenopausal (amenorrhea following cancer therapy does not rule

out childbearing potential) for at least 24 consecutive months (i.e. had menses at any

time in the preceding 24 consecutive months). An FCBP participating in the study must:

- Have 2 negative pregnancy tests as verified by the investigator prior to starting

IMP (unless the screening pregnancy test is done within 72 hours of Cycle 1 Day

1). She must agree to ongoing pregnancy testing during the course of the study

and after end of treatment (EOT).

- If sexually active, agree to use, and be able to comply with, highly effective

contraception** without interruption, 5 weeks prior to starting IMP, during

treatment with IMP (including dose interruptions), and for 12 weeks after

discontinuation of IMP. ** Highly effective contraception is defined in this

protocol as the following (information also appears in the ICF): Hormonal

contraception (e.g. birth control pills, injection, implant, transdermal patch,

vaginal ring), intrauterine device, tubal ligation, or a partner with a vasectomy

9. Male subjects must agree to use a condom, defined as a male latex condom or nonlatex

condom NOT made out of natural (animal) membrane (e.g. polyurethane), during sexual

contact with a pregnant female or an FCBP while participating in the study, during

dose interruptions, and for at least 12 weeks following IMP discontinuation, even if

he has undergone a successful vasectomy

10. Subject is willing and able to adhere to the study visit schedule and other protocol

requirements

Exclusion Criteria:

1. Prior therapy with disease modifying agents other than HMA or LEN for underlying MDS

disease

2. Previously treated with either luspatercept or sotatercept

3. Secondary MDS, i.e. MDS that is known to have arisen as the result of chemical injury

or treatment with chemotherapy and/or radiation for other diseases

4. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies,

or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding

• Iron deficiency to be determined by local laboratory via serum ferritin ≤ 15 μg/L

and additional testing if clinically indicated (e.g. calculated transferrin saturation

[iron/total iron binding capacity ≤ 20%] or bone marrow aspirate stain for iron)

5. Prior allogeneic or autologous stem cell transplant

6. Known history of diagnosis of acute myeloid leukemia (AML)

7. Use of any of the following within 5 weeks prior to the first dose of the IMP in this

study:

- Anticancer cytotoxic chemotherapeutic agent or treatment

- Corticosteroid, except for subjects on a stable or decreasing dose for ≥ 1 week

prior to the first dose of IMP for medical conditions other than MDS ICT, except

for subjects on a stable or decreasing dose for at least 8 weeks prior to the

first dose of IMP

- Other RBC hematopoietic growth factors (e.g. interleukin [IL]-3)

- Investigational drug or device, or approved therapy for investigational use. If

the half-life of the previous study drug is known, the use of it within 5 times

the half-life prior to the first dose of IMP or within 5 weeks, whichever is

longer, is excluded

8. Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure

(DBP) ≥ 100 mmHg despite adequate treatment

9. Platelet count < 30,000/μL (30 × 109/L)

10. Estimated glomerular filtration rate or creatinine clearance < 40 mL/min

11. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) or

alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≥ 3.0 ×

upper limit of normal (ULN)

12. Total bilirubin ≥ 2.0 × ULN

- Higher levels are acceptable if these can be attributed to active RBC precursor

destruction within the bone marrow (i.e. ineffective erythropoiesis) or in the

presence of known history of Gilbert Syndrome

- Subjects are excluded if there is evidence of autoimmune hemolytic anemia

manifested as a corrected reticulocyte count of > 2% with either a positive

Coombs test or over 50% indirect bilirubin

13. Prior history of malignancies, other than MDS, unless the subject is free of the

disease (including completion of any active or adjuvant treatment for prior

malignancy) for ≥ 5 years. However, subjects with the following history/concurrent

conditions are allowed:

- Basal or squamous cell carcinoma of the skin

- Carcinoma in situ of the cervix

- Carcinoma in situ of the breast

- Incidental histologic finding of prostate cancer (T1a or T1b using the tumor,

nodes, metastasis clinical staging system)

14. Major surgery within 8 weeks prior to the first dose of IMP. Subjects must be

completely recovered from any previous surgery prior to the first dose of IMP

15. History of stroke, deep venous thrombosis, pulmonary or arterial embolism within 6

months prior to the first dose of IMP

16. Pregnant or breast-feeding females

17. Myocardial infarction, uncontrolled angina, uncontrolled heart failure, or

uncontrolled cardiac arrhythmia as determined by the investigator within 6 months

prior to the first dose of IMP. Subjects with a known ejection fraction of ˂ 35%,

confirmed by a local echocardiography or multigated acquisition scan (MUGA) performed

within 6 months prior to the first dose of IMP, are excluded

18. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing

signs/symptoms related to the infection without improvement despite appropriate

antibiotics, antiviral therapy, and/or other treatment), known human immunodeficiency

virus (HIV), known evidence of active infectious hepatitis B, and/or known evidence of

active hepatitis C

19. History of severe allergic or anaphylactic reactions or hypersensitivity to

recombinant proteins or excipients in the IMP

20. Subject is in custody by order of an authority or a court of law

21. Participation in another interventional clinical study within the last 3 months prior

to signing the ICF or simultaneous participation in other clinical studies

22. Close affiliation with the investigator (e.g. a close relative) or persons working at

the study site

23. Subject is an employee of the sponsor or involved Contract research Organization (CRO)

24. Criteria which in the opinion of the investigator preclude participation for

scientific reasons, for reasons of compliance, or for reasons of the subject's safety

Studien-Rationale

Primary outcome:

1. RBC-TI rate according to IWG 2018 modified criteria (Time Frame - from Week 1 through Week 24):
Evaluation of RBC-TI rate of luspatercept for the treatment of anemia due to IPSS-R very low-, low-, or intermediate-risk MDS in subjects with ring sideroblasts (RS) who require RBC transfusions (according to IWG 2018 criteria).

Secondary outcome:

1. RBC-TI rate according to IWG 2006 criteria (Time Frame - from Week 1 through Week 24 and through Week 52):
RBC-TI rates according to IWG 2006 criteria (Weeks 1-24 and Weeks 1-52) will be estimated and 97.5% lower confidence limit will be calculated analogously to the primary endpoint.

2. Median time to RBC-TI (Time Frame - Week 1 through Week 24 and through Week 52):
Time to RBC-TI will be summarized only for subjects who achieve RBC TI ≥ 8 weeks on treatment. It is defined as the time between start of IMP and the date onset of TI is first observed (i.e, Day 1 of 56 days without any RBC transfusions).

3. Median Duration of RBC-TI (Time Frame - Week 1 through Week 24 and through Week 52):
Duration of RBC-TI will be determined only for subjects who achieve RBC TI ≥ 8 weeks on treatment. Duration of RBC-TI is defined as the longest RBC-TI period during the treatment period. Duration of response starts at the date onset of TI is first observed (i.e, Day 1 of 56 days without any RBC transfusions). Transfusion response ends on the day of the first transfusion given after response is documented. Subjects who maintain RBC-TI through EOT will be censored at the date of treatment discontinuation or death, whichever occurs first.

4. Change in RBC units transfused (Time Frame - Week 9 through Week 24 and Week 37 through Week 52):
Total number of RBC units transfused over a fixed 16-weeks period (weeks 9-24; weeks 37-52) will be compared to the total number of RBC units transfused in the 16 weeks immediately prior to first IMP.

5. Proportion of subjects achieving mean Hb increase ≥ 1.0 g/dL (Time Frame - Week 1 through Week 24 and through Week 52):
Hemoglobin (Hb) increase ≥ 1.0 g/dL is defined as proportion of subjects with ≥ 1.0 g/dL Hb increase compared to baseline that is sustained over any consecutive 56-day period within a specified timeframe in the absence of RBC transfusions.

6. Proportion of subjects achieving modified hematologic improvement - erythroids (mHI-E) per IWG 2006 criteria (Time Frame - Week 1 through Week 24 and through Week 52)

7. Proportion of subjects achieving hematologic improvement - neutrophils (HI-N) per IWG 2006 criteria (Time Frame - Week 1 through Week 24 and through Week 52)

8. Proportion of subjects achieving hematologic improvement - platelets (HI-P) per IWG 2006 criteria (Time Frame - Week 1 through Week 24 and through Week 52)

9. Mean change in serum ferritin (Time Frame - Week 9 through Week 24 and Week 37 through Week 52):
Mean change in serum ferritin (Week 9-24; Weeks 37-52) is calculated as the difference of post-baseline mean serum ferritin and baseline mean serum ferritin.

10. Mean Change in Mean Daily Dose of Iron Chelation Therapy (ICT) (Time Frame - Week 9 through Week 24 and Week 37 through Week 52):
The change in daily dose for each subject is calculated as the difference of post-baseline mean daily dose and baseline mean daily dose.

11. Proportion of subjects with progression to AML (acute myeloid leukemia) (Time Frame - Week 1 to Week 52):
Time to progression to AML is defined as the time between baseline (day1 of IMP administration) and first diagnosis of AML as per WHO classification of ≥ 20% blasts in peripheral blood or bone marrow.

12. Overall survival (Time Frame - Week 1 to Week 52):
Overall survival (OS) is defined as the time between start of IMP and death.

13. Change in PRO (Time Frame - Week 1 to Week 52 and to EOT):
In order to evaluate the Change in PRO questionnaires (from Week 1 to Week 52 and to EOT) utilizing EORTC QLQ-C30, changes from baseline in overall score and sub-scores will be calculated.

14. Change in PerfO (Time Frame - Week 1 to Week 52 and to EOT):
In order to evaluate the Change in PerfO questionnaires (from Week 1 to Week 52 and to EOT) utilizing "Timed Up and Gotest" (TUG), changes from baseline in overall score and sub-scores will be calculated.

Geprüfte Regime

Luspatercept (Reblozyl):
Once 1.75 mg/kg on Day 1 of each 21-day cycle for 24 weeks (9 cycles)

Quelle: ClinicalTrials.gov

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