Study Evaluating Combination of Luspatercept in LR-MDS Without RS Having Failed or Being Ineligible to ESA
A Randomized Phase I/ II Multicenter Study Evaluating Combination of Luspatercept in LR-MDS Without RS Having Failed or Being Ineligible to ESA
2 other identifiers
interventional
150
2 countries
40
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2022
Longer than P75 for phase_1
40 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 20, 2021
CompletedFirst Posted
Study publicly available on registry
January 6, 2022
CompletedStudy Start
First participant enrolled
May 18, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 19, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 19, 2029
March 5, 2026
March 1, 2026
6.6 years
December 20, 2021
March 3, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Part A : Dose-finding study
To determine the optimal dose level in terms of both toxicity and efficacy for luspatercept + EPO
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
At week 25
Secondary Outcomes (3)
Response rate
3 months
Response duration
24 months
Overall survival
30 months
Study Arms (2)
Arm A (Luspatercept alone)
EXPERIMENTALPatients 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).
Arm B (Luspatercept + EPREX)
EXPERIMENTALPatients 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
Interventions
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
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
Eligibility Criteria
You may qualify if:
- 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
- +3 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celgenecollaborator
- Groupe Francophone des Myelodysplasieslead
Study Sites (40)
CHU Amiens-Picardie
Amiens, 80054, France
Clinique de l'Europe
Amiens, 80090, France
CHU Angers
Angers, 49933, France
Centre Hospitalier Victor Dupouy
Argenteuil, 95107, France
CH Henri Duffaut d'Avignon
Avignon, 84000, France
Centre Hospitalier de la Côte Basque
Bayonne, 64109, France
Hôpital Avicenne
Bobigny, 93009, France
Hôpital Privé Sévigné
Cesson-Sévigné, 35510, France
CHU de Grenoble
Grenoble, 38043, France
Centre Hospitalier de Versailles
Le Chesnay, 78150, France
Hôpital Bicêtre
Le Kremlin-Bicêtre, 94270, France
CH Le Mans
Le Mans, 72037, France
CHRU de Lille - Hôpital Claude Huriez
Lille, 59037, France
CHRU de Limoges - Hôpital Dupuytren
Limoges, 87042, France
Centre Hospitalier de Mont de Marsan
Mont-de-Marsan, 40000, France
CHU Saint Eloi
Montpellier, 34295, France
CHU Nantes - Hôtel Dieu
Nantes, 44093, France
Hôpital privé du Confluent
Nantes, 44277, France
CHU de Nice - Hôpital Archet 1
Nice, 06202, France
CHU de Nîmes
Nîmes, 30029, France
CHR d'Orléans
Orléans, 45067, France
Hôpital Saint Louis
Paris, 75010, France
Hôpital Cochin
Paris, 75014, France
Hôpital Necker
Paris, 75015, France
CHU de Bordeaux - Hôpital Haut-Lévêque
Pessac, 33604, France
Centre Hospitalier de Périgueux
Périgueux, 24019, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495, France
CHU de Poitiers
Poitiers, 86021, France
Hôpital NOVO
Pontoise, 95300, France
Centre Hospitalier de Cornouaille
Quimper, 29107, France
CHU de Rennes - Hôpital Pontchaillou
Rennes, 35033, France
Centre Henri Becquerel
Rouen, 76038, France
Institut de Cancérologie et d'Hématologie Universitaire de Saint-Etienne
Saint-Priest-en-Jarez, 42271, France
Strasbourg Oncologie Libérale Clinique Sainte Anne
Strasbourg, 67000, France
CHU Toulouse - IUCT Oncopole
Toulouse, 31059, France
CHU de Tours - Hôpital Bretonneau
Tours, 37000, France
Centre Hospitalier de Valence
Valence, 26000, France
CHRU Nancy - Hôpitaux de Brabois
Vandœuvre-lès-Nancy, 54511, France
IRCCS
Candiolo, 10060, Italy
AOU Careggi
Florence, 50134, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lionel ADES, Pr.
Hôpital Saint Louis
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 20, 2021
First Posted
January 6, 2022
Study Start
May 18, 2022
Primary Completion (Estimated)
December 19, 2028
Study Completion (Estimated)
June 19, 2029
Last Updated
March 5, 2026
Record last verified: 2026-03