Study Evaluating Combination of Luspatercept in LR-MDS Without RS Having Failed or Being Ineligible to ESA

NCT ID: NCT05181735

Last Updated: 2025-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-18

Study Completion Date

2029-06-19

Brief Summary

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Study of the combination of luspatercept in low-risk myelodysplastic syndrom (LR-MDS) without ring sideroblasts (RS) having failed or being ineligible to ESA

Detailed Description

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Part A of the trial=Dose-finding Study: Determination the optimal dose level in terms of both toxicity and efficacy for luspatercept + ESA

Part B : Determination of the superiority and efficacy of the association Luspatercept+ESA (erythroipoiesis Stimulating Agent) over luspatercept alone in patients with lower risk MDS who failed to achieve a response or who subsequently relapsed after ESA, wihtout disease progression

Conditions

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MDS Myelodysplastic Syndromes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (Luspatercept alone)

Patients will receive Luspatercept 1mg/kg (every 3 weeks) with titration up to max of 1.75mg/kg, subcutaneously on day 1 of each 21 day cycle (every three weeks).

Group Type EXPERIMENTAL

Luspatercept Injection [Reblozyl]

Intervention Type DRUG

All patients will receive Luspatercept subcutaneously on day 1 of each 21 day cycle (every 3 weeks) at the selected dose according to part A : 1.75mg/kg or 1.33 mg/kg or 0.8 mg/kg

Arm B (Luspatercept + EPREX)

Patients will receive Luspatercept (at the selected dose according to part A) subcutaneously on day 1 of each 21 day cycle (every three weeks) AND Epoetin alfa: At the selected dose (in part A) per week, subcutaneously, every week

Doses schedules Part A :

* Level 1 : Luspatercept 0.8 mg/kg + EPREX 30000 UI
* Level 2 : Luspatercept 1.33 mg/kg + EPREX 30000 UI
* Level 3 : Luspatercept 1.75mg/kg + EPREX 30000 UI
* Level 4 : Luspatercept 1.75mg/kg + EPREX 60000 UI

Group Type EXPERIMENTAL

Luspatercept Injection [Reblozyl]

Intervention Type DRUG

All patients will receive Luspatercept subcutaneously on day 1 of each 21 day cycle (every 3 weeks) at the selected dose according to part A : 1.75mg/kg or 1.33 mg/kg or 0.8 mg/kg

Eprex

Intervention Type DRUG

Epoietin alfa will be adminstered as a subcutaneous injection at the selected dose according to part A : 30 000 UI/week or 60 000 UI/week, every week

Interventions

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Luspatercept Injection [Reblozyl]

All patients will receive Luspatercept subcutaneously on day 1 of each 21 day cycle (every 3 weeks) at the selected dose according to part A : 1.75mg/kg or 1.33 mg/kg or 0.8 mg/kg

Intervention Type DRUG

Eprex

Epoietin alfa will be adminstered as a subcutaneous injection at the selected dose according to part A : 30 000 UI/week or 60 000 UI/week, every week

Intervention Type DRUG

Other Intervention Names

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ACE-536 Epoietin alfa

Eligibility Criteria

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Inclusion Criteria

Patients must meet all of the following criteria to participate in the study:

* Myelodysplastic syndrome according to current WHO classification
* Age ≥ 18 years
* Patients with lower risk MDS according to IPSS classification (LOW, INT-1) without RS who failed to achieved a response or who subsequently relapse after ESA (at least 60000 U EPO-a over at least 12weeks or equivalent), without disease progression (or ineligible to ESA defined by EPO \> 500 UI/l)
* Hemoglobin \< 9 gr/dl or Transfusion dependant (at least 3 RBCs in 16 wk in at least 2 transfusion episodes)
* Non del(5q) syndrome
* Adequat renal function, defined by creatinine less than 1.5 times the upper limit of normal, creatinine clearance ≥ 40 mL/min (MDRD formula).
* Adequat liver function, defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal.
* Patient is not known to be refractory to platelet transfusions.
* Written informed consent.
* Patient must understand and voluntarily sign consent form.
* Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements.
* ECOG performance status 0-2 at the time of screening.
* A FCBP (female of childbearing potential) for this study was defined as a sexually mature woman who: (1) had not undergone a hysterectomy or bilateral oophorectomy; or (2) had not been naturally postmenopausal (amenorrhea following cancer therapy did not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). A FCBP participating in the study must:

* Have had 2 negative pregnancy tests as verified by the investigator prior to starting IP (unless the screening pregnancy test was done within 72 hours of Cycle 1 Day 1). She must have had agreed to ongoing a monthly pregnancy testing during the course of the study and after EOT
* If sexually active, agreed to have used, and been able to comply with, highly effective contraception\*\* without interruption, 5 weeks prior to starting IP, during treatment with IP (including dose interruptions), and for 12 weeks after discontinuation of IP.
* \*\* Highly effective contraception was defined in this protocol as the following (information also appeared in the ICF): Hormonal contraception (eg, birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device, tubal ligation (tying your tubes), or a partner with a vasectomy
* Male subjects must: Have agreed to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane), during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions, and for at least 12 weeks following IP discontinuation, even if he had undergone a successful vasectomy

Exclusion Criteria

A patient meeting any of the following criteria is not eligible to participate in the study:

* Severe infection or any other uncontrolled severe condition.
* Uncontrolled hypertension
* Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months.
* del(5q) syndrome
* Use of investigational agents within 30 days or any anticancer therapy (including IMiD) within 2 weeks before the study entry with the exception of hydroxyurea. The patient must have recovered at least a grade 1 from all acute toxicity from any previous therapy.
* Use of EPO within 4 weeks before the study entry
* Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma, or carcinoma in situ of the cervix or breast.
* Patient already enrolled in another therapeutic trial of an investigational drug.
* Known HIV infection or active hepatitis B or C.
* Women who are or could become pregnant or who are currently breastfeeding.
* Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form.
* Patient eligible for allogeneic stem cell transplantation.
* Known allergies to luspatercept or EPO or any of its excipients.
* No affiliation to a health insurance system.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Groupe Francophone des Myelodysplasies

OTHER

Sponsor Role lead

Celgene

INDUSTRY

Sponsor Role collaborator

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lionel ADES, Pr.

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint Louis

Locations

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CHU Amiens-Picardie

Amiens, , France

Site Status RECRUITING

Clinique de l'Europe

Amiens, , France

Site Status NOT_YET_RECRUITING

CHU Angers

Angers, , France

Site Status RECRUITING

Centre Hospitalier Victor Dupouy

Argenteuil, , France

Site Status RECRUITING

CH Henri Duffaut d'Avignon

Avignon, , France

Site Status RECRUITING

Centre Hospitalier de la Côte Basque

Bayonne, , France

Site Status NOT_YET_RECRUITING

Hôpital Avicenne

Bobigny, , France

Site Status RECRUITING

Hôpital Privé Sévigné

Cesson-Sévigné, , France

Site Status RECRUITING

CHU de Grenoble

Grenoble, , France

Site Status RECRUITING

Centre Hospitalier de Versailles

Le Chesnay, , France

Site Status NOT_YET_RECRUITING

Hôpital Bicêtre

Le Kremlin-Bicêtre, , France

Site Status RECRUITING

CH Le Mans

Le Mans, , France

Site Status RECRUITING

CHRU de Lille - Hôpital Claude Huriez

Lille, , France

Site Status NOT_YET_RECRUITING

CHRU de Limoges - Hôpital Dupuytren

Limoges, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier de Mont de Marsan

Mont-de-Marsan, , France

Site Status NOT_YET_RECRUITING

CHU Saint Eloi

Montpellier, , France

Site Status RECRUITING

CHU Nantes - Hôtel Dieu

Nantes, , France

Site Status RECRUITING

Hôpital privé du Confluent

Nantes, , France

Site Status RECRUITING

CHU de Nice - Hôpital Archet 1

Nice, , France

Site Status RECRUITING

CHU de Nîmes

Nîmes, , France

Site Status RECRUITING

CHR d'Orléans

Orléans, , France

Site Status RECRUITING

Hôpital Saint Louis

Paris, , France

Site Status RECRUITING

Hôpital Cochin

Paris, , France

Site Status NOT_YET_RECRUITING

Hôpital Necker

Paris, , France

Site Status RECRUITING

CHU de Bordeaux - Hôpital Haut-Lévêque

Pessac, , France

Site Status RECRUITING

Centre Hospitalier de Périgueux

Périgueux, , France

Site Status RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status NOT_YET_RECRUITING

CHU de Poitiers

Poitiers, , France

Site Status NOT_YET_RECRUITING

Hôpital NOVO

Pontoise, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier de Cornouaille

Quimper, , France

Site Status NOT_YET_RECRUITING

CHU de Rennes - Hôpital Pontchaillou

Rennes, , France

Site Status RECRUITING

Centre Henri Becquerel

Rouen, , France

Site Status RECRUITING

Institut de Cancérologie et d'Hématologie Universitaire de Saint-Etienne

Saint-Priest-en-Jarez, , France

Site Status RECRUITING

Strasbourg Oncologie Libérale Clinique Sainte Anne

Strasbourg, , France

Site Status RECRUITING

CHU Toulouse - IUCT Oncopole

Toulouse, , France

Site Status RECRUITING

CHU de Tours - Hôpital Bretonneau

Tours, , France

Site Status RECRUITING

Centre Hospitalier de Valence

Valence, , France

Site Status RECRUITING

CHRU Nancy - Hôpitaux de Brabois

Vandœuvre-lès-Nancy, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Fatiha CHERMAT

Role: CONTACT

+33 1 71 20 70 59

Karine LEMARIE

Role: CONTACT

+33 1 71 20 70 54

Facility Contacts

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Etienne PAUBELLE, Dr

Role: primary

+33 3 22 45 59 14

Bérengère GRUSON, MD

Role: primary

+33 3 60 12 76 87

Sylvain THEPOT, Dr

Role: primary

+33 2 41 35 44 66

Benjamin PAPOULAR, Dr

Role: primary

+33 1 34 23 20 16

Borhane SLAMA, Dr

Role: primary

+33 4 32 75 93 94

Delphine MARTINEAU, MD

Role: primary

+33 5 59 44 38 32

Thorsten BRAUN, Pr

Role: primary

+33 1 48 95 70 51

Anne-Violaine DONCKER, MD

Role: primary

+33 2 23 21 05 50

Mathieu MEUNIER, Dr

Role: primary

+33 4 76 76 62 77

Anne Laure TAKSIN, Dr

Role: primary

+33 1 39 63 92 60

Pirayeh EFTEKHARI, Dr

Role: primary

+33 1 45 21 25 34

Kamel LARIBI, Dr

Role: primary

+33 2 43 43 43 61

Laure GOURSAUD, Dr

Role: primary

+33 3 20 44 42 90

Marie-Pierre GOURIN, Dr

Role: primary

+33 5 55 05 66 42

Reza TABRIZI, Dr

Role: primary

+33 5 58 05 11 62

Franciane PAUL, MD

Role: primary

+33 4 67 33 22 54

Alice GARNIER, Dr

Role: primary

+33 2 40 08 32 71

Jacques DELAUNAY, MD

Role: primary

+33 2 28 27 21 16

Thomas CLUZEAU, Pr

Role: primary

+33 4 92 03 58 39

Stefan WICKENHAUSER, Dr

Role: primary

+33 4 66 68 40 33

Ali ARAR, Dr

Role: primary

+33 2 38 22 95 46

Lionel ADES, Pr.

Role: primary

+33 1 71 20 70 21

Lise WILLEMS, Dr

Role: primary

+33 1 58 41 21 20

Cécile BALLY, Dr

Role: primary

+33 1 44 49 53 42

Sophie DIMICOLI-SALAZAR, Dr

Role: primary

+33 5 57 65 65 11

Claire CALMETTES, Dr

Role: primary

+33 5 53 45 25 85

Maël HEIBLIG, MD

Role: primary

+33 4 78 86 22 34

Jose Miguel TORREGROSA-DIAZ, Dr

Role: primary

+33 5 49 44 44 44 ext. 45415

Riad BENRAMDANE, Dr

Role: primary

+33 1 30 75 47 41

Lenaïg LE CLECH, MD

Role: primary

+33 2 98 52 67 31

Stanislas NIMUBONA, Dr

Role: primary

+33 2 99 28 42 91

Aspasia STAMATOULLAS, Dr

Role: primary

+33 2 32 08 22 88

Silvia Maria BEZSERA, Dr

Role: primary

+33 4 77 91 71 46

Anaïse BLOUET, Dr

Role: primary

+33 3 88 45 37 50

Thibault COMONT, Dr

Role: primary

+33 5 31 15 62 66

Emmanuel GYAN, Pr

Role: primary

+33 2 47 25 87 78

Clémence SANTANA, MD

Role: primary

+33 4 75 75 25 92

Maud D'AVENI-PINEY, Pr

Role: primary

+33 3 83 15 32 82

Other Identifiers

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2021-000596-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

COMBOLA

Identifier Type: -

Identifier Source: org_study_id

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