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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05181735
Other study ID # COMBOLA
Secondary ID 2021-000596-37
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date May 18, 2022
Est. completion date November 19, 2027

Study information

Verified date January 2024
Source Groupe Francophone des Myelodysplasies
Contact Fatiha CHERMAT
Phone +33 1 71 20 70 59
Email fatiha.chermat-ext@aphp.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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


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


Recruitment information / eligibility

Status Recruiting
Enrollment 150
Est. completion date November 19, 2027
Est. primary completion date May 19, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
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
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

Locations

Country Name City State
France CHU Amiens-Picardie Amiens
France CHU Angers Angers
France Centre Hospitalier Victor Dupouy Argenteuil
France CH Henri Duffaut d'Avignon Avignon
France Centre Hospitalier de la Côte Basque Bayonne
France Hôpital Avicenne Bobigny
France CHU de Caen Côte de Nacre Caen
France CHU de Grenoble Grenoble
France Hôpital Bicêtre Le Kremlin-Bicêtre
France CH Le Mans Le Mans
France Hôpital Saint Vincent de Paul Lille
France CHRU de Limoges - Hôpital Dupuytren Limoges
France Institut Paoli Calmettes Marseille
France Centre Hospitalier de Mont de Marsan Mont-de-Marsan
France CHU Nantes - Hôtel Dieu Nantes
France CHU de Nice - Hôpital Archet 1 Nice
France CHU de Nîmes Nîmes
France CHR d'Orléans Orléans
France Hôpital Cochin Paris
France Hôpital Necker Paris
France Hôpital Saint Louis Paris
France Centre Hospitalier de Périgueux Périgueux
France CHU de Bordeaux - Hôpital Haut-Lévêque Pessac
France Centre Hospitalier Lyon Sud Pierre-Bénite
France CHU de Poitiers Poitiers
France CHU de Rennes - Hôpital Pontchaillou Rennes
France Centre Henri Becquerel Rouen
France Institut de Cancérologie et d'Hématologie Universitaire de Saint-Etienne Saint-Priest-en-Jarez
France CHU Toulouse - IUCT Oncopole Toulouse
France CHU de Tours - Hôpital Bretonneau Tours
France CHRU Nancy - Hôpitaux de Brabois VandÅ“uvre-lès-Nancy

Sponsors (2)

Lead Sponsor Collaborator
Groupe Francophone des Myelodysplasies Celgene

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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 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 3 months
Secondary Response duration Duration of response ends with date loss of response, relapse or death whichever occurs first 24 months
Secondary 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 30 months
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