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

January 2, 2024 updated by: Groupe Francophone des Myelodysplasies

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Amiens, France, 80054
        • Not yet recruiting
        • CHU Amiens-Picardie
        • Contact:
        • Principal Investigator:
          • Etienne PAUBELLE, Dr
      • Angers, France, 49933
        • Recruiting
        • Chu Angers
        • Contact:
        • Principal Investigator:
          • Sylvain THEPOT, Dr
      • Argenteuil, France, 95107
        • Recruiting
        • Centre Hospitalier Victor Dupouy
        • Contact:
        • Principal Investigator:
          • Benjamin PAPOULAR, Dr
      • Avignon, France, 84000
        • Not yet recruiting
        • CH Henri Duffaut d'Avignon
        • Contact:
        • Principal Investigator:
          • Borhane SLAMA, Dr
      • Bayonne, France, 64109
        • Not yet recruiting
        • Centre Hospitalier de la Côte Basque
        • Principal Investigator:
          • Anne BANOS, Dr
        • Contact:
      • Bobigny, France, 93009
        • Not yet recruiting
        • Hôpital Avicenne
        • Contact:
        • Principal Investigator:
          • Thorsten BRAUN, Dr
      • Caen, France, 14033
        • Not yet recruiting
        • CHU de Caen Côte de Nacre
        • Contact:
        • Principal Investigator:
          • Stéphane CHEZE, Dr
      • Grenoble, France, 38043
        • Recruiting
        • CHU de Grenoble
        • Contact:
        • Principal Investigator:
          • Mathieu MEUNIER, Dr
      • Le Kremlin-Bicêtre, France, 94270
        • Not yet recruiting
        • Hôpital Bicêtre
        • Contact:
        • Principal Investigator:
          • Pirayeh EFTEKHARI, Dr
      • Le Mans, France, 72037
        • Not yet recruiting
        • CH Le Mans
        • Contact:
        • Principal Investigator:
          • Kamel LARIBI, Dr
      • Lille, France, 59020
        • Not yet recruiting
        • Hopital Saint Vincent De Paul
        • Contact:
        • Principal Investigator:
          • Laurent PASCAL, Dr
      • Limoges, France, 87042
        • Not yet recruiting
        • CHRU de Limoges - Hôpital Dupuytren
        • Contact:
        • Principal Investigator:
          • Marie-Pierre GOURIN, Dr
      • Marseille, France, 13273
        • Not yet recruiting
        • Institut Paoli Calmettes
        • Principal Investigator:
          • Norbert VEY, Pr
        • Contact:
      • Mont-de-Marsan, France, 40000
        • Not yet recruiting
        • Centre Hospitalier de Mont de Marsan
        • Contact:
        • Principal Investigator:
          • Reza TABRIZI, Dr
      • Nantes, France, 44093
        • Recruiting
        • CHU Nantes - Hôtel Dieu
        • Contact:
        • Principal Investigator:
          • Alice GARNIER, Dr
      • Nice, France, 06202
        • Recruiting
        • CHU de Nice - Hôpital Archet 1
        • Principal Investigator:
          • Thomas Cluzeau, Pr
        • Contact:
      • Nîmes, France, 30029
        • Not yet recruiting
        • CHU de Nimes
        • Contact:
        • Principal Investigator:
          • Stefan WICKENHAUSER, Dr
      • Orléans, France, 45067
        • Not yet recruiting
        • CHR d'Orléans
        • Contact:
        • Principal Investigator:
          • Ali ARAR, Dr
      • Paris, France, 75010
        • Recruiting
        • Hôpital Saint louis
        • Contact:
        • Principal Investigator:
          • Lionel ADES, Pr.
      • Paris, France, 75014
        • Not yet recruiting
        • Hôpital Cochin
        • Contact:
        • Principal Investigator:
          • Lise Willems, Dr
      • Paris, France, 75015
        • Not yet recruiting
        • Hopital Necker
        • Contact:
        • Principal Investigator:
          • Cécile BALLY, Dr
      • Pessac, France, 33604
        • Not yet recruiting
        • CHU de Bordeaux - Hopital Haut-Lévêque
        • Contact:
        • Principal Investigator:
          • Sophie DIMICOLI-SALAZAR, Dr
      • Pierre-Bénite, France, 69495
        • Not yet recruiting
        • Centre Hospitalier Lyon Sud
        • Contact:
        • Principal Investigator:
          • Gaëlle FOSSARD, Dr
      • Poitiers, France, 86021
        • Not yet recruiting
        • CHU de Poitiers
        • Contact:
        • Principal Investigator:
          • Jose Miguel TORREGROSA-DIAZ, Dr
      • Périgueux, France, 24019
        • Recruiting
        • Centre Hospitalier de Perigueux
        • Contact:
        • Principal Investigator:
          • Claire CALMETTES, Dr
      • Rennes, France, 35033
        • Not yet recruiting
        • CHU de Rennes - Hôpital Pontchaillou
        • Contact:
        • Principal Investigator:
          • Stanislas NIMUBONA, Dr
      • Rouen, France, 76038
        • Recruiting
        • Centre Henri Becquerel
        • Contact:
        • Principal Investigator:
          • Aspasia STAMATOULLAS, Dr
      • Saint-Priest-en-Jarez, France, 42271
        • Not yet recruiting
        • Institut de Cancérologie et d'Hématologie Universitaire de Saint-Etienne
        • Contact:
        • Principal Investigator:
          • Silvia Maria BEZSERA, Dr
      • Toulouse, France, 31059
        • Recruiting
        • CHU Toulouse - IUCT Oncopole
        • Contact:
        • Principal Investigator:
          • Thibault COMONT, Dr
      • Tours, France, 37000
        • Recruiting
        • CHU de Tours - Hôpital Bretonneau
        • Contact:
        • Principal Investigator:
          • Emmanuel GYAN, Pr
      • Vandœuvre-lès-Nancy, France, 54511
        • Recruiting
        • CHRU Nancy - Hôpitaux de Brabois
        • Contact:
        • Principal Investigator:
          • Maud D'AVENI-PINEY, Dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (Luspatercept alone)
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).
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
Other Names:
  • ACE-536
Experimental: Arm B (Luspatercept + EPREX)

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
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
Other Names:
  • ACE-536
Drug: 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
Other Names:
  • Epoietin alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A : Dose-finding study
Time Frame: Evaluation of Dose-limiting toxicity (DLT) at Day 21 of cycle 1 for non-hematological toxicity , up to day 42 for hematological toxicity
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
Time Frame: At week 25
To determine, at Week 25, the superiority and efficacy of luspatercept + ESA over luspatecept alone
At week 25

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: 3 months
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
Response duration
Time Frame: 24 months
Duration of response ends with date loss of response, relapse or death whichever occurs first
24 months
Overall survival
Time Frame: 30 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Groupe Francophone des Myelodysplasies

Collaborators

Celgene

Investigators

  • Principal Investigator: Lionel ADES, Pr., Hôpital Saint louis

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2022

Primary Completion (Estimated)

May 19, 2027

Study Completion (Estimated)

November 19, 2027

Study Registration Dates

First Submitted

December 20, 2021

First Submitted That Met QC Criteria

December 20, 2021

First Posted (Actual)

January 6, 2022

Study Record Updates

Last Update Posted (Estimated)

January 3, 2024

Last Update Submitted That Met QC Criteria

January 2, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COMBOLA
  • 2021-000596-37 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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