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

Myelodysplastic Syndromes Clinical Trial

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

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
• 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
• 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.

Related Conditions & MeSH terms

• MDS
• Myelodysplastic Syndromes

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	Vandœuvre-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