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Myelodysplastic SyndromesPhase 2PhoenixNCT05924100

Efficacy and Safety of Luspatercept for the Treatment of Anemia Due to MDS With del5q, Refractory/Resistant/Intolerant to Prior Treatments, RBC-TD

A Phase 2 study testing Luspatercept Injection [Reblozyl] in people with Myelodysplastic Syndromes and Del(5Q), run by Associazione Qol-one at 23 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes, Del(5Q), Anemia
What is being tested?
Luspatercept Injection [Reblozyl]
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
23 sitesItaly
Study dates
3 Nov 2022to 3 Dec 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  • Documented diagnosis of MDS with del5q according to 2018 WHO classification
  • 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
  • Refractory or intolerant to, or ineligible for, prior ESA treatment
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  • 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.
  • 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
  • Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2
  • 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.
  • 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.
  • Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

Who cannot join

  • P53 mutation at screening
  • 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.
  • Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
  • 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:
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  • 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)

Trial locations and contacts

23 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Esther N Oliva, MD contact

+393298699514

trials@qol-one.org

23 sites in 1 country

Italy23 sites, 23 recruiting

  • A.O. SS. Antonio e Biagio e Cesare Arrigo Ospedale Civile

    Alessandria

    Monia Marchetti

    Monia Marchetti

    Not yet recruiting

  • A.O.U. Ospedali Riuniti

    Ancona

    Antonella Poloni, a.poloni@univpm.it

    Antonella Poloni

    Recruiting

  • A.O. S. Giuseppe Moscati

    Avellino

    Antonio Volpe

    Antonio Volpe

    Not yet recruiting

  • Ospedale degli Infermi

    Biella

    Andrea Castelli

    Andrea Castelli

    Not yet recruiting

  • A.O.U. G. Rodolico San Marco

    Catania

    Giuseppe A Palumbo

    Giuseppe A Palumbo

    Not yet recruiting

  • ARNAS Garibaldi, PO Nesima

    Catania

    Stefana Impera

    Stefana Impera

    Not yet recruiting

  • ASL TO 4 - Ospedale Chivasso

    Chivasso

    Emanuela Messa

    Emanuela Messa

    Not yet recruiting

  • Azienda Ospedaliera Annunziata

    Cosenza

    Ernesto Vigna

    Ernesto Vigna

    Not yet recruiting

  • A.O.U. Careggi

    Florence

    Valeria Santini

    Valeria Santini

    Not yet recruiting

  • A.O.U. Federico II

    Naples

    Fabrizio Pane

    Fabrizio Pane

    Not yet recruiting

  • A.O.U. Maggiore della Carità

    Novara

    Andrea Patriarca, andrea.patriarca@uniupo.it

    Andrea Patriarca

    Not yet recruiting

  • A.O.U. Policlinico Paolo Giaccone

    Palermo

    Sergio Siragusa

    Sergio Siragusa

    Not yet recruiting

  • Ospedale Civile Spirito Santo

    Pescara

    Prassede Salutari

    Prassede Salutari

    Not yet recruiting

  • Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli

    Reggio Calabria, 89133

    Esther N Oliva, +393298699514, trials@qol-one.org

    Esther N Oliva, MD

    Recruiting

  • IRCCS di Reggio Emilia

    Reggio Emilia

    Isabella Capodanno, Isabella.Capodanno@ausl.re.it

    Isabella Capodanno

    Not yet recruiting

  • Ospedale S. Eugenio

    Roma

    Pasquale Niscola

    Pasquale Niscola

    Not yet recruiting

  • Policlinico Tor Vergata

    Roma

    Maria T Voso

    Maria T Voso

    Not yet recruiting

  • Policlinico Umberto I

    Roma

    Massimo Breccia

    Massimo Breccia

    Not yet recruiting

  • A.O.U. San Giovanni di Dio e Ruggì D'Aragona

    Salerno

    Carmine Selleri

    Carmine Selleri

    Not yet recruiting

  • Casa Sollievo della Sofferenza IRCCS

    San Giovanni Rotondo

    Grazia Sanpaolo

    Grazia Sanpaolo

    Not yet recruiting

  • AO Santa Maria di Terni

    Terni

    Marina Liberati, marina.liberati@unipg.it

    Marina Liberati

    Not yet recruiting

  • A.O. Città della Salute e della Scienza

    Torino

    Chiara Frairia

    Chiara Frairia

    Not yet recruiting

  • ASU Giuliano Isontina

    Trieste

    Francesco Zaja

    Francesco Zaja

    Not yet recruiting

Other trials in Italy

About this study

Official title: Efficacy and Safety of Luspatercept for the Treatment of Anemia Due to Myelodysplastic Syndromes With del5q, Refractory/Resistant/Intolerant to Prior Treatments, Who Require Red Blood Cell Transfusions

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.

Read more

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.

Being tested
Luspatercept Injection [Reblozyl]
Keywords
MDS with Del(5Q)
Medical subject headings
Myelodysplastic Syndromes, Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Luspatercept Injection [Reblozyl]Drug

    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.

Study groups in NCT05924100
Study groupRoleWhat they receive
LuspaterceptExperimentalNot described
Receives: Drug: Luspatercept Injection [Reblozyl]

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. RBC Transfusion Independence

    Proportion of subjects who are RBC TI for 8 weeks over the first 24 weeks from trial entry

    Measured: 24 WEEKS

Secondary outcomes (10)

  1. Safety and tolerability of Luspatercept measured as frequency and severity of adverse events occurred and assessed by CTCAE v. 5.0

    Type, frequency, severity of AEs. The adverse events occurring in the subjects enrolled in the study will be evaluated according to CTCAE v5.0 Furthermore, the relationship between adverse events and treatment with luspatercept will be evaluated

    Measured: 5 years

  2. RBC-TI in long term

    Proportion of subjects who are RBC TI for 8 weeks over the first 48 weeks from trial entry and over the 30 months

    Measured: 5 years

  3. Duration of RBC-TI

    Maximum duration of RBC transfusion independence for subjects who achieve RBC TI ≥ 8 weeks

    Measured: 2 years

  4. Reduction in RBC transfusions

    Mean change in total pRBC units transfused over a rolling 8-week period and proportion achievieng HI-E (reduction in ≥ 4 units in the preceding 8 weeks in those with baseline transfusion burden of ≥8 units in 8 preceding weeks)

    Measured: 24 weeks

  5. Increase in hemoglobin

    Mean change in hb levels from baseline and proportion achieving HI-E (gain in Hb ≥1.5 g/dL)

    Measured: 2 years

  6. Change in quality of life scores with QOL-E questionnaire

    Scores of QOL-E questionnaire from baseline and proportion achieving meaningful clinical important difference). Higher values indicate better quality of life

    Measured: 2 years

  7. Change in quality of life scores with HM-PRO questionnaire

    Scores of HM-PRO questionnaire from baseline and proportion achieving meaningful clinical important difference). Lower values indicate better quality of life

    Measured: 2 years

  8. Change in Serum Ferritin

    Mean change of the value of serum ferritin from baseline.

    Measured: 2 years

  9. Change in iron chelation therapy use

    Mean change of dose of iron chelation therapy use from baseline

    Measured: 2 years

  10. Time to RBC TI

    Time to achieving first RBC TI ≥ 8 weeks in the first 24 weeks

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2023
  2. Study start3 Nov 2022
  3. Primary completion3 Dec 2024 (estimated)
  4. Study completion3 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05924100
Sponsor's protocol ID
QOL-ONE Phoenix
Acronym
Phoenix
Status last verified
Nov 2024
First submitted
8 Jun 2023
Last updated
18 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Luspatercept Injection [Reblozyl] in people with Myelodysplastic Syndromes and Del(5Q), run by Associazione Qol-one at 23 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Esther N Oliva, MD (+393298699514, trials@qol-one.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

RBC Transfusion Independence (time frame: 24 WEEKS). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05924100.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2024.

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