MDSPhase 1/2NCT05181735
Study Evaluating Combination of Luspatercept in LR-MDS Without RS Having Failed or Being Ineligible to ESA
A Phase 1/2 study testing Luspatercept Injection [Reblozyl] and Eprex in people with MDS and Myelodysplastic Syndromes, run by Groupe Francophone des Myelodysplasies at 41 sites in 2 countries.
Trial summary
Study of the combination of luspatercept in low-risk myelodysplastic syndrom (LR-MDS) without ring sideroblasts (RS) having failed or being ineligible to ESA Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MDS, Myelodysplastic Syndromes
- What is being tested?
- Luspatercept Injection [Reblozyl] and Eprex
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 41 sitesin 2 countries
- Study dates
- 18 May 2022to 19 Jun 2029
- Phase
- Phase 1/2
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
- 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
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
41 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
41 sites in 2 countries
France39 sites, 39 recruiting
- Recruiting
CHU Amiens-Picardie
Amiens, 80054
Etienne PAUBELLE, Dr, +33 3 22 45 59 14, paubelle.etienne@chu-amiens.fr
Etienne PAUBELLE, Dr
- Not yet recruiting
Clinique de l'Europe
Amiens, 80090
Bérengère GRUSON, MD, +33 3 60 12 76 87, bgruson@vivalto-sante.com
Bérengère GRUSON, MD
- Recruiting
CHU Angers
Angers, 49933
Sylvain THEPOT, Dr, +33 2 41 35 44 66, sylvain.thepot@chu-angers.fr
Sylvain THEPOT, Dr
- Recruiting
Centre Hospitalier Victor Dupouy
Argenteuil, 95107
Benjamin PAPOULAR, Dr, +33 1 34 23 20 16, benjamin.papoular@ch-argenteuil.fr
Benjamin PAPOULAR, Dr
- Recruiting
CH Henri Duffaut d'Avignon
Avignon, 84000
Borhane SLAMA, Dr, +33 4 32 75 93 94, bslama@ch-avignon.fr
Borhane SLAMA, Dr
- Not yet recruiting
Centre Hospitalier de la Côte Basque
Bayonne, 64109
Delphine MARTINEAU, MD, +33 5 59 44 38 32, dmartineau@ch-cotebasque.fr
Delphine MARTINEAU, MD
- Recruiting
Hôpital Avicenne
Bobigny, 93009
Thorsten BRAUN, Pr, +33 1 48 95 70 51, thorsten.braun@aphp.fr
Thorsten BRAUN, Dr
- Recruiting
Hôpital Privé Sévigné
Cesson-Sévigné, 35510
Anne-Violaine DONCKER, MD, +33 2 23 21 05 50, violainedoncker@gmail.com
Anne-Violaine DONCKER, MD
- Not yet recruiting
Hôpital de Compiègne
Compiègne, 60200
Louis-Nicolas DUMEIGNIL, MD, +33 3 44 23 64 96, ln.dumeignil@ch-compiegnenoyon.fr
Louis-Nicolas DUMEIGNIL, MD
- Recruiting
CHU de Grenoble
Grenoble, 38043
Mathieu MEUNIER, Dr, +33 4 76 76 62 77, MMeunier2@chu-grenoble.fr
Mathieu MEUNIER, Dr
- Recruiting
Centre Hospitalier de Versailles
Le Chesnay, 78150
Anne Laure TAKSIN, Dr, +33 1 39 63 92 60, altaksin@ght78sud.fr
Anne Laure TAKSIN, Dr
- Recruiting
Hôpital Bicêtre
Le Kremlin-Bicêtre, 94270
Pirayeh EFTEKHARI, Dr, +33 1 45 21 25 34, pirayeh.eftekhari@aphp.fr
Pirayeh EFTEKHARI, Dr
- Recruiting
CH Le Mans
Le Mans, 72037
Kamel LARIBI, Dr, +33 2 43 43 43 61, klaribi@ch-lemans.fr
Kamel LARIBI, Dr
- Not yet recruiting
CHRU de Lille - Hôpital Claude Huriez
Lille, 59037
Laure GOURSAUD, Dr, +33 3 20 44 42 90, laure.goursaud@chu-lille.fr
Laure GOURSAUD, Dr
- Not yet recruiting
CHRU de Limoges - Hôpital Dupuytren
Limoges, 87042
Marie-Pierre GOURIN, Dr, +33 5 55 05 66 42, marie-pierre.gourin@chu-limoges.fr
Marie-Pierre GOURIN, Dr
- Not yet recruiting
Centre Hospitalier de Mont de Marsan
Mont-de-Marsan, 40000
Reza TABRIZI, Dr, +33 5 58 05 11 62, reza.tabrizi@ch-mdm.fr
Reza TABRIZI, Dr
- Recruiting
CHU Saint Eloi
Montpellier, 34295
Franciane PAUL, MD, +33 4 67 33 22 54, f-paul@chu-montpellier.fr
Franciane PAUL, MD
- Recruiting
CHU Nantes - Hôtel Dieu
Nantes, 44093
Alice GARNIER, Dr, +33 2 40 08 32 71, Alice.GARNIER@chu-nantes.fr
Alice GARNIER, Dr
- Recruiting
Hôpital privé du Confluent
Nantes, 44277
Jacques DELAUNAY, MD, +33 2 28 27 21 16, jacques.delaunay@groupeconfluent.fr
Jacques DELAUNAY, MD
- Recruiting
CHU de Nice - Hôpital Archet 1
Nice, 06202
Thomas CLUZEAU, Pr, +33 4 92 03 58 39, cluzeau.t@chu-nice.fr
Thomas CLUZEAU, Pr
- Recruiting
CHU de Nîmes
Nîmes, 30029
Stefan WICKENHAUSER, Dr, +33 4 66 68 40 33, stefan.WICKENHAUSER@chu-nimes.fr
Stefan WICKENHAUSER, Dr
- Recruiting
CHR d'Orléans
Orléans, 45067
Ali ARAR, Dr, +33 2 38 22 95 46, ali.arar@chr-orleans.fr
Ali ARAR, Dr
- Recruiting
Hôpital Saint Louis
Paris, 75010
Lionel ADES, Pr., +33 1 71 20 70 21, lionel.ades@aphp.fr
Lionel ADES, Pr.
- Not yet recruiting
Hôpital Cochin
Paris, 75014
Lise WILLEMS, Dr, +33 1 58 41 21 20, lise.willems@aphp.fr
Lise Willems, Dr
- Recruiting
Hôpital Necker
Paris, 75015
Cécile BALLY, Dr, +33 1 44 49 53 42, cecile.bally@aphp.fr
Cécile BALLY, Dr
- Recruiting
Centre Hospitalier de Périgueux
Périgueux, 24019
Claire CALMETTES, Dr, +33 5 53 45 25 85, claire.calmettes@ch-perigueux.fr
Claire CALMETTES, Dr
- Recruiting
CHU de Bordeaux - Hôpital Haut-Lévêque
Pessac, 33604
Sophie DIMICOLI-SALAZAR, Dr, +33 5 57 65 65 11, sophie.dimicoli-salazar@chu-bordeaux.fr
Sophie DIMICOLI-SALAZAR, Dr
- Not yet recruiting
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
Maël HEIBLIG, MD, +33 4 78 86 22 34, mael.heiblig@chu-lyon.fr
Maël HEIBLIG, MD
- Recruiting
CHU de Poitiers
Poitiers, 86021
Jose Miguel TORREGROSA-DIAZ, Dr, +33 5 49 44 44 44 ext. 45415, jose-miguel.torregrosa-diaz@chu-poitiers.fr
Jose Miguel TORREGROSA-DIAZ, Dr
- Not yet recruiting
Hôpital NOVO
Pontoise, 95300
Riad BENRAMDANE, Dr, +33 1 30 75 47 41, riad.benramdane@ght-novo.fr
Riad BENRAMDANE, Dr
- Not yet recruiting
Centre Hospitalier de Cornouaille
Quimper, 29107
Lenaïg LE CLECH, MD, +33 2 98 52 67 31, l.leclech@ch-cornouaille.fr
Lenaïg LE CLECH, MD
- Recruiting
CHU de Rennes - Hôpital Pontchaillou
Rennes, 35033
Stanislas NIMUBONA, Dr, +33 2 99 28 42 91, stanislas.nimubona@chu-rennes.fr
Stanislas NIMUBONA, Dr
- Recruiting
Centre Henri Becquerel
Rouen, 76038
Aspasia STAMATOULLAS, Dr, +33 2 32 08 22 88, aspasia.stamatoullas@chb.unicancer.fr
Aspasia STAMATOULLAS, Dr
- Recruiting
Institut de Cancérologie et d'Hématologie Universitaire de Saint-Etienne
Saint-Priest-en-Jarez, 42271
Silvia Maria BEZSERA, Dr, +33 4 77 91 71 46, silviamaria.bezsera@chu-st-etienne.fr
Silvia Maria BEZSERA, Dr
- Recruiting
Strasbourg Oncologie Libérale Clinique Sainte Anne
Strasbourg, 67000
Anaïse BLOUET, Dr, +33 3 88 45 37 50, ablouet@solcrr.org
Anaïse BLOUET, Dr
- Recruiting
CHU Toulouse - IUCT Oncopole
Toulouse, 31059
Thibault COMONT, Dr, +33 5 31 15 62 66, Comont.Thibault@iuct-oncopole.fr
Thibault COMONT, Dr
- Recruiting
CHU de Tours - Hôpital Bretonneau
Tours, 37000
Emmanuel GYAN, Pr, +33 2 47 25 87 78, emmanuel.gyan@univ-tours.fr
Emmanuel GYAN, Pr
- Recruiting
Centre Hospitalier de Valence
Valence, 26000
Clémence SANTANA, MD, +33 4 75 75 25 92, clemence.santana@ch-valence.fr
Clémence SANTANA, MD
- Recruiting
CHRU Nancy - Hôpitaux de Brabois
Vandœuvre-lès-Nancy, 54511
Maud D'AVENI-PINEY, Pr, +33 3 83 15 32 82, m.daveni-piney@chru-nancy.fr
Maud D'AVENI-PINEY, Dr
Italy2 sites, 2 recruiting
- Recruiting
IRCCS
Candiolo, 10060
Elena CRISA, MD, +390119933096, elena.crisa@ircc.it
Elena CRISA, MD
- Recruiting
AOU Careggi
Florence, 50134
Valeria SANTINI, Pr., +39 055 2758020, valeria.santini@unifi.it
Valeria SANTINI, Pr.
About this study
Official title: A Randomized Phase I/ II Multicenter Study Evaluating Combination of Luspatercept in LR-MDS Without RS Having Failed or Being Ineligible to ESA
Study of the combination of luspatercept in low-risk myelodysplastic syndrom (LR-MDS) without ring sideroblasts (RS) having failed or being ineligible to ESA
Read the detailed description
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
- MDS, Myelodysplastic Syndromes
- Being tested
- Luspatercept Injection [Reblozyl], Eprex
- Keywords
- MDS, LR-MDS, Luspatercept, Eprex, ESA
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Luspatercept Injection [Reblozyl]Drug
Also called ACE-536
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
EprexDrug
Also called Epoietin alfa
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
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Luspatercept alone) | Experimental | 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). Receives: Drug: Luspatercept Injection [Reblozyl] |
| Arm B (Luspatercept + EPREX) | Experimental | 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 Receives: Drug: Luspatercept Injection [Reblozyl]; Drug: Eprex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A : Dose-finding study
To determine the optimal dose level in terms of both toxicity and efficacy for luspatercept + EPO
Measured: Evaluation of Dose-limiting toxicity (DLT) at Day 21 of cycle 1 for non-hematological toxicity , up to day 42 for hematological toxicity
Part B : Benefit of the association over the monotherapy
To determine, at Week 25, the superiority and efficacy of luspatercept + ESA over luspatecept alone
Measured: At week 25
Secondary outcomes (3)
Response rate
To determine the response rate (complete response (CR) +Partial Response (PR) + stable disease with Hematological Improvment (HI) according to IWG 2006 criteria) in each arm
Measured: 3 months
Response duration
Duration of response ends with date loss of response, relapse or death whichever occurs first
Measured: 24 months
Overall survival
Overall survival time ends for patients who die during the follow up period with the date of death and for patients who do not die during the follow up period with the date when the patient was last seen to be alive
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2022
- Study start18 May 2022
- Primary completion19 Dec 2028 (estimated)
- Study completion19 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MDSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Groupe Francophone des Myelodysplasies
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene
- Responsible party
- Sponsor
- Investigators
- Lionel ADES, Pr., Principal investigator, Hôpital Saint Louis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05181735
- Sponsor's protocol ID
- COMBOLA
- Other IDs
- 2021-000596-37
- Status last verified
- Sep 2026
- First submitted
- 20 Dec 2021
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No