Clinical trial NCT05181735: Study Evaluating Combination of Luspatercept in LR-MDS Without RS Having Failed or Being Ineligible to ESA
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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: MDS
Myelodysplastic Syndromes
Keywords: MDS
LR-MDS
Luspatercept
Eprex
ESA
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
Collaborators: name: Celgene
First posted: 2022-01-06
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Part A : Dose-finding study
timeFrame: Evaluation of Dose-limiting toxicity (DLT) at Day 21 of cycle 1 for non-hematological toxicity , up to day 42 for hematological toxicity
measure: Part B : Benefit of the association over the monotherapy
timeFrame: At week 25
Secondary outcomes:
measure: Response rate
timeFrame: 3 months
measure: Response duration
timeFrame: 24 months
measure: Overall survival
timeFrame: 30 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens-Picardie
city: Amiens
country: France
facility: Clinique de l'Europe
city: Angers
country: France
facility: CHU Angers
city: Argenteuil
country: France
facility: Centre Hospitalier Victor Dupouy
city: Avignon
country: France
facility: CH Henri Duffaut d'Avignon
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Cesson-Sévigné
country: France
facility: Hôpital Privé Sévigné
city: Grenoble
country: France
facility: CHU de Grenoble
city: Le Chesnay
country: France
facility: Centre Hospitalier de Versailles
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre
city: Le Mans
country: France
facility: CH Le Mans
city: Lille
country: France
facility: CHRU de Lille - Hôpital Claude Huriez
city: Limoges
country: France
facility: CHRU de Limoges - Hôpital Dupuytren
city: Mont-de-Marsan
country: France
facility: Centre Hospitalier de Mont de Marsan
city: Montpellier
country: France
facility: CHU Saint Eloi
city: Nantes
country: France
facility: CHU Nantes - Hôtel Dieu
city: Nantes
country: France
facility: Hôpital privé du Confluent
city: Nice
country: France
facility: CHU de Nice - Hôpital Archet 1
city: Nîmes
country: France
facility: CHU de Nîmes
city: Orléans
country: France
facility: CHR d'Orléans
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Necker
city: Pessac
country: France
facility: CHU de Bordeaux - Hôpital Haut-Lévêque
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers
city: Pontoise
country: France
facility: Hôpital NOVO
city: Périgueux
country: France
facility: Centre Hospitalier de Périgueux
city: Quimper
country: France
facility: Centre Hospitalier de Cornouaille
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie et d'Hématologie Universitaire de Saint-Etienne
city: Strasbourg
country: France
facility: Strasbourg Oncologie Libérale Clinique Sainte Anne
city: Toulouse
country: France
facility: CHU Toulouse - IUCT Oncopole
city: Tours
country: France
facility: CHU de Tours - Hôpital Bretonneau
city: Valence
country: France
facility: Centre Hospitalier de Valence
city: Vandœuvre-lès-Nancy
country: France
facility: CHRU Nancy - Hôpitaux de Brabois
Study officials:
affiliation: Hôpital Saint Louis
name: Lionel ADES, Pr.
role: PRINCIPAL_INVESTIGATOR
References: