Trial Title:
Efficacy and Safety of Luspatercept for the Treatment of Anemia Due to MDS With del5q, Refractory/Resistant/Intolerant to Prior Treatments, RBC-TD
NCT ID:
NCT05924100
Condition:
Myelodysplastic Syndromes
Del(5Q)
Anemia
Transfusion-dependent Anemia
Conditions: Official terms:
Preleukemia
Anemia
Myelodysplastic Syndromes
Syndrome
Luspatercept
Conditions: Keywords:
MDS with Del(5Q)
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Luspatercept Injection [Reblozyl]
Description:
Eligible subjects will receive luspatercept (ACE-536): starting dose of 1.0 mg/kg
subcutaneous injection every 3 weeks (21 days; Q3W). Dose levels can be increased in a
stepwise manner beyond the starting dose to 1.33 mg/kg, and up to a maximum of 1.75 mg/kg
(with a maximum total dose of 168 mg).
All subjects who have received at least one dose of luspatercept should undergo follow-up
evaluations after day 169 with Assessment visits every 24 weeks (168 days) up to 2 years
to evaluate evidence of clinical benefit.
Arm group label:
Luspatercept
Summary:
Myelodysplastic syndromes, primarily affecting older adults, are a heterogeneous group of
clonal disorders of hematopoietic stem cells characterized by ineffective hematopoiesis
that manifest clinically as anemia, neutropenia, and/or thrombocytopenia of variable
severity; these often result in RBC- transfusion dependent (TD) anemia, increased risk of
infection, and/or hemorrhage, as well as a potential to progress to acute myeloid
leukemia (AML).
Lenalidomide is approved for red blood cell transfusion-dependent (RBC TD) anemia due to
low-risk myelodysplastic syndromes (MDS) with a chromosome 5q deletion (del5q) with or
without additional cytogenetic abnormalities. About one third of patients are
refractory/resistant/intolerant and will require further treatment options.
Luspatercept (ACE-536), an erythroid maturation agent, is a recombinant fusion protein
consisting of a modified form of the extracellular domain (ECD) of the human activin
receptor type IIB (ActRIIB) linked to the Fc portion of human immunoglobulin G1
(IgG1-Fc). Luspatercept acts on endogenous inhibitors of late-stage erythropoiesis (eg,
growth differentiation factor 11, GDF11) to increase release of mature erythrocytes into
circulation. Nonclinical data have demonstrated that luspatercept binds to negative
regulators governing late-stage erythroid development to inhibit their action, thereby
promoting the maturation of erythrocytes in the bone marrow.
Luspatercept is indicated for the treatment of adult patients with transfusion-dependent
anaemia associated with beta-thalassaemia and due to very low, low and intermediate-risk
MDS with ring sideroblasts, who had an unsatisfactory response to or are ineligible for
erythropoietin-based-therapy. It is not indicated for other MDS subtypes. Unfortunately,
patients with MDS with del5q refractory/resistant/intolerant to lenalidomide are excluded
from clinical trials that evaluate novel treatments for the anemia of RBC TD lower risk
MDS. Therefore, treatment of anemia in such patients is an unmet need.
QOL-ONE Phoenix is a Phase 2, multicenter, single arm, prospective study. The primary
objective of the study is to evaluate the effect of luspatercept on RBC TI in subjects
with MDS with del5q with IPSS-R very low, low, or intermediate risk and < 5% bone marrow
blasts, resistant/refractory/intolerant to lenalidomide and who require RBC transfusions.
The study is divided into a Screening Period, a 2-year Treatment Period and a 3-year
Follow-up Period.
Primary objective is to evaluate the effect of luspatercept on RBC TI (lack of
transfusions for 8 consecutive weeks within the first 24 weeks) in subjects with MDS with
del5q with IPSS-R very low, low, or intermediate risk and < 5% bone marrow blasts,
resistant/refractory/intolerant to lenalidomide and RBC TD.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.
2. Documented diagnosis of MDS with del5q according to 2018 WHO classification
3. IPSS-R classification (Greenberg, 2012) of very low, low, or intermediate risk
disease, and:
- < 5% blasts in bone marrow
- Peripheral blood WBC count <13,000/μL
4. Refractory or intolerant to, or ineligible for, prior ESA treatment
5. If previously treated with ESAs or granulocyte colony-stimulating factor (G-CSF),
both agents must have been discontinued ≥ 4 weeks prior to date of screening.
6. Refractory or intolerant to, or ineligible for, prior lenalidomide treatment, as
defined by any one of the following:
- Refractory to prior lenalidomide treatment for at least 4 cycles; -
documentation of non-response or response that is no longer maintained (HI-E)
- Intolerant to prior lenalidomide treatment - documentation of discontinuation
of lenalidomide at any time after introduction due to intolerance or an adverse
event
- lenalidomide ineligible -platelet counts below 50000/mmc or absolute neutrophil
count below 500/mmc at the start of treatment
- lenalidomide must have been discontinued ≥ 4 weeks prior to date of screening.
Requires RBC transfusions, as documented by the following criteria:
- average transfusion requirement of ≥ 2 units/8 weeks of pRBCs confirmed for a
minimum of 16 weeks immediately preceding enrolment.
- Hb levels at the time of or within 7 days prior to administration of a RBC
transfusion must have been ≤ 10.0 g/dL in order for the transfusion to be
counted towards meeting eligibility criteria. RBC transfusions administered
when Hb levels were > 10.0 g/dL and/or RBC transfusions administered for
elective surgery will not qualify as a required transfusion for the purpose of
meeting eligibility criteria.
- no consecutive 56-day period that was RBC transfusion-free during the 16 weeks
immediately preceding screening
7. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2
8. Females of childbearing potential, defined as a sexually mature woman who: 1) has
not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally
postmenopausal (amenorrhea following cancer therapy 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:
- Have two negative pregnancy tests as verified by the Investigator prior to
starting study therapy (unless the screening pregnancy test was done within 72
hours of C1D1). Refer to Section 6.1 for additional details. She must agree to
ongoing pregnancy testing during the course of the study, and after the end of
study treatment.
- If sexually active, agree to use, and be able to comply with, highly effective
contraception without interruption, 5 weeks prior to starting investigational
product, during the study therapy (including dose interruptions), and for 12
weeks after discontinuation of study therapy.
9. Male subjects must:
- Agree to use a condom, defined as a male latex condom or non latex condom not
made out of natural (animal) membrane (for example, polyurethane), 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 12
weeks following investigational product 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. P53 mutation at screening
2. Prior therapy with disease modifying agents for underlying MDS disease
(hypomethylating agents)
- subjects who previously received HMA may be enrolled at the investigator's
discretion contingent that the subject received no more than 1 dose of HMA).
The last dose must be ≥ 5 weeks from the date of screening.
3. Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
4. Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury
or treatment with chemotherapy and/or radiation for other diseases. 5 Known
clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or
autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
6. Prior allogeneic or autologous stem cell transplant 7. Known history of diagnosis of
AML 8. Use of any of the following within 5 weeks prior to study entry:
- anticancer cytotoxic chemotherapeutic agent or treatment
- corticosteroid, except for subjects on a stable or decreasing dose for ≥ 1 week
prior to study entry for medical conditions other than MDS
- iron-chelating agents, except for subjects on a stable or decreasing dose for at
least 8 weeks prior to screening
- other RBC hematopoietic growth factors
- investigational drug or device, or approved therapy for investigational use. If the
half- life of the previous investigational product is known, use within 5 times the
half- life prior to screening or within 5 weeks, whichever is longer is excluded. 9.
Uncontrolled hypertension, defined as repeated elevations of diastolic blood
pressure (DBP) ≥ 100 mmHg despite adequate treatment. 10. Estimated glomerular
filtration rate (eGFR) or creatinine clearance < 40 mL/min.
11. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase or
alanine aminotransferase/serum glutamic pyruvic transaminase ≥ 3.0 x upper
limit of normal (ULN) 12. Total bilirubin ≥ 2.0 x ULN.
- higher levels are acceptable if these can be attributed to active red blood cell
precursor destruction within the bone marrow (ie, ineffective erythropoiesis) or in
the presence of known history of Gilbert Syndrome.
- subjects are excluded if there is evidence of autoimmune hemolytic anemia 13. Prior
history of malignancies, other than MDS, unless the subject has been 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 [TNM] clinical staging system)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
A.O. SS. Antonio e Biagio e Cesare Arrigo Ospedale Civile
Address:
City:
Alessandria
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Monia Marchetti
Investigator:
Last name:
Monia Marchetti
Email:
Principal Investigator
Facility:
Name:
A.O.U. Ospedali Riuniti
Address:
City:
Ancona
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Antonella Poloni
Email:
a.poloni@univpm.it
Investigator:
Last name:
Antonella Poloni
Email:
Principal Investigator
Facility:
Name:
A.O. S. Giuseppe Moscati
Address:
City:
Avellino
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Antonio Volpe
Investigator:
Last name:
Antonio Volpe
Email:
Principal Investigator
Facility:
Name:
Ospedale degli Infermi
Address:
City:
Biella
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Andrea Castelli
Investigator:
Last name:
Andrea Castelli
Email:
Principal Investigator
Facility:
Name:
A.O.U. G. Rodolico San Marco
Address:
City:
Catania
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Giuseppe A Palumbo
Investigator:
Last name:
Giuseppe A Palumbo
Email:
Principal Investigator
Facility:
Name:
ARNAS Garibaldi, PO Nesima
Address:
City:
Catania
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Stefana Impera
Investigator:
Last name:
Stefana Impera
Email:
Principal Investigator
Facility:
Name:
ASL TO 4 - Ospedale Chivasso
Address:
City:
Chivasso
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Emanuela Messa
Investigator:
Last name:
Emanuela Messa
Email:
Principal Investigator
Facility:
Name:
Azienda Ospedaliera Annunziata
Address:
City:
Cosenza
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Ernesto Vigna
Investigator:
Last name:
Ernesto Vigna
Email:
Principal Investigator
Facility:
Name:
A.O.U. Careggi
Address:
City:
Firenze
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Valeria Santini
Investigator:
Last name:
Valeria Santini
Email:
Principal Investigator
Facility:
Name:
A.O.U. Federico II
Address:
City:
Napoli
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Fabrizio Pane
Investigator:
Last name:
Fabrizio Pane
Email:
Principal Investigator
Facility:
Name:
A.O.U. Maggiore della Carità
Address:
City:
Novara
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Andrea Patriarca
Email:
andrea.patriarca@uniupo.it
Investigator:
Last name:
Andrea Patriarca
Email:
Principal Investigator
Facility:
Name:
A.O.U. Policlinico Paolo Giaccone
Address:
City:
Palermo
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Sergio Siragusa
Investigator:
Last name:
Sergio Siragusa
Email:
Principal Investigator
Facility:
Name:
Ospedale Civile Spirito Santo
Address:
City:
Pescara
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Prassede Salutari
Investigator:
Last name:
Prassede Salutari
Email:
Principal Investigator
Facility:
Name:
Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
Address:
City:
Reggio Calabria
Zip:
89133
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Esther N Oliva
Phone:
+393298699514
Email:
trials@qol-one.org
Investigator:
Last name:
Esther N Oliva, MD
Email:
Principal Investigator
Facility:
Name:
IRCCS di Reggio Emilia
Address:
City:
Reggio Emilia
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Isabella Capodanno
Email:
Isabella.Capodanno@ausl.re.it
Investigator:
Last name:
Isabella Capodanno
Email:
Principal Investigator
Facility:
Name:
Ospedale S. Eugenio
Address:
City:
Roma
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Pasquale Niscola
Investigator:
Last name:
Pasquale Niscola
Email:
Principal Investigator
Facility:
Name:
Policlinico Tor Vergata
Address:
City:
Roma
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Maria T Voso
Investigator:
Last name:
Maria T Voso
Email:
Principal Investigator
Facility:
Name:
Policlinico Umberto I
Address:
City:
Roma
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Massimo Breccia
Investigator:
Last name:
Massimo Breccia
Email:
Principal Investigator
Facility:
Name:
A.O.U. San Giovanni di Dio e Ruggì D'Aragona
Address:
City:
Salerno
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Carmine Selleri
Investigator:
Last name:
Carmine Selleri
Email:
Principal Investigator
Facility:
Name:
Casa Sollievo della Sofferenza IRCCS
Address:
City:
San Giovanni Rotondo
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Grazia Sanpaolo
Investigator:
Last name:
Grazia Sanpaolo
Email:
Principal Investigator
Facility:
Name:
AO Santa Maria di Terni
Address:
City:
Terni
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Marina Liberati
Email:
marina.liberati@unipg.it
Investigator:
Last name:
Marina Liberati
Email:
Principal Investigator
Facility:
Name:
A.O. Città della Salute e della Scienza
Address:
City:
Torino
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Chiara Frairia
Investigator:
Last name:
Chiara Frairia
Email:
Principal Investigator
Facility:
Name:
ASU Giuliano Isontina
Address:
City:
Trieste
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Francesco Zaja
Investigator:
Last name:
Francesco Zaja
Email:
Principal Investigator
Start date:
November 3, 2022
Completion date:
November 3, 2028
Lead sponsor:
Agency:
Associazione Qol-one
Agency class:
Other
Source:
Associazione Qol-one
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05924100
