Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
177
Countries
1
Sites
17
High-risk myeloïd malignancies
To assess the 2-year progression free survival rates in patients with high-risk myeloid ma-lignancies following HSCT using different dose levels of IV Busulfan (BX3 and BX4) com-bined with fludarabine and thymoglobuline as conditioning therapy
Key facts
- Sponsor
- Institut Paoli Calmettes
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04], Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 5 Nov 2024 → 27 May 2026
- Decision date (initial)
- 2024-11-05
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- French ministry of health, DGOS
External identifiers
- EU CT number
- 2024-516435-27-00
- EudraCT number
- 2013-001935-36
- WHO UTN
- U1111-1310-6025
- ClinicalTrials.gov
- NCT01985061
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Pharmacogenetic, Pharmacokinetic, Efficacy
To assess the 2-year progression free survival rates in patients with high-risk myeloid ma-lignancies following HSCT using different dose levels of IV Busulfan (BX3 and BX4) com-bined with fludarabine and thymoglobuline as conditioning therapy
Secondary objectives 4
- To document full donor chimerism achievement, hematologic recovery and response to treatment rates
- To document acute GVHD, chronic GVHD, relapse and non-relapse mortality cumulative incidences
- To document overall survival
- To document safety
Conditions and MedDRA coding
High-risk myeloïd malignancies
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 27.0 | PT | 10028533 | Myelodysplastic syndrome | 100000004864 |
| 21.0 | LLT | 10000886 | Acute myeloid leukemia | 10029104 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Patients with poor prognosis myeloid malignancies in particular : myelodysplasic syndrome, AML beyond CR1 regardless of the cytogenetic or molecular abnormalities or CR1 AML after double induction regardless of the cytogenetic or molecular abnormalities or CR1 AML with no criteria for favorable risk according to the ELN classification
- Adult patients aged ≥ 50 years up to 65 or < 50 years not eligible for myeloablative conditioning regimen based on TBI or double alkylating agent combinations
- Availability of a HLA identical sibling or matched unrelated donor (10/10)
- Affiliation to social security
- Written Informed Consent
Exclusion criteria 7
- History of previous Allo-HSCT
- HIV positivity
- Signs of chronic active hepatitis B and/or C
- Evolutive psychiatric disease
- Concomitant neoplasic disease
- Pregnant or lactating woman or without contraception (for child bearing potential women)
- Usual contra-indications for Allo-HSCT
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Time to progression or death
Secondary endpoints 6
- Time to death and cause of death
- Time to acute and chronic GVHD according to the NIH classification and relapse
- Response to treatment
- Hematological recovery defined as the achievement 500 ANC and 50 000 platelets (without transfusion)
- Full donor chimerism achievement at M1, M2, M3
- Occurrence of grade 3-4 adverse events according the CTC AE v4.0 scale within 6 months after conditionning
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Busulfan 6 mg/ml concentrate for solution for infusion
PRD9789219 · Product
- Active substance
- Busulfan
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 3.2 mg/kg milligram(s)/kilogram
- Max total dose
- 12.8 mg/kg milligram(s)/kilogram
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01AB01 — BUSULFAN
- Marketing authorisation
- PL 20075/0445
- MA holder
- ACCORD HEALTHCARE LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Not authorised
Auxiliary 2
Fludarabine Accord Healthcare 25 mg/ml solution à diluer pour solution injectable /pour perfusion
PRD1794895 · Product
- Active substance
- Fludarabine Phosphate
- Substance synonyms
- FLUDARABINE 5'-MONOPHOSPHATE, FLUDARABINE MONOPHOSPHATE
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 30 mg/m2 milligram(s)/sq. meter
- Max total dose
- 150 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 5 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BB05 — FLUDARABINE
- Marketing authorisation
- BE462391
- MA holder
- ACCORD HEALTHCARE B.V.
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
THYMOGLOBULINE 5 mg/ml, poudre pour solution pour perfusion
PRD440932 · Product
- Active substance
- Rabbit Anti-Human Thymocyte Immunoglobulin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- IV INFUSION
- Max daily dose
- 2.5 mg/kg milligram(s)/kilogram
- Max total dose
- 5 mg/kg milligram(s)/kilogram
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- L04AA04 — ANTITHYMOCYTE IMMUNOGLOBULIN (RABBIT)
- Marketing authorisation
- 34009 570 281 8 3
- MA holder
- SANOFI B.V.
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Institut Paoli Calmettes
- Sponsor organisation
- Institut Paoli Calmettes
- Address
- 232 Boulevard De Sainte Marguerite, Bp 156 Bp 156
- City
- Marseille
- Postcode
- 13009
- Country
- France
Scientific contact point
- Organisation
- Institut Paoli Calmettes
- Contact name
- Pr Didier BLAISE
Public contact point
- Organisation
- Institut Paoli Calmettes
- Contact name
- Marina LAROSA
Locations
1 EU/EEA country · 17 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ended | 177 | 17 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Hospitalier Universitaire De Bordeaux
Hématologie et Thérapie Cellulaire, Avenue De Magellan, 33600, Pessac
Institut Paoli Calmettes
Hématologie et Transplantation, 232 Boulevard De Sainte Marguerite, Bp 156, Marseille
Hopital Saint Antoine
Hématologie clinique et Thérapie Cellulaire, 184 Rue Du Faubourg Saint Antoine, 75571, Paris Cedex 12
CHRU Jean Minjoz
Hématologie, 3 Boulevard Alexandre Fleming, 25030, Besançon
Hôpital l'Archet 1
Hématologie clinique, CHU NIce, 151 route de Saint-Antoine de Ginestière, Nice
CHU Saint Eloi
Hématologie, 8 0Avnenue Augustin Fliche, 34295, Montpellier
Oncopole Claudius Regaud
Hématologie, 1 Avenue Irene Joliot Curie, 31059, Toulouse Cedex 9
Hospital Hotel Dieu
Hématologie clinique, 1 Place Alexis Ricordeau, 44000, Nantes
Hospices Civils De Lyon
Hématologie clinique, 165 Chemin Du Grand Revoyet, 69310, Pierre Benite
Centre Hospitalier Universitaire De Lille
Hématologie, 2 Avenue Oscar Lambret, Cs 70001, Lille Cedex
Centre Hospitalier Universitaire D'Angers
Maladies du sang, 4 Rue Larrey, 49100, Angers
CHU d'Estaing
Hématologie clinique et thérapie cellulaire, 1 place Lucie et Raymond Aubrax, 63100, Clermont-Ferrand
Centre Hospitalier Universitaire Grenoble Alpes
Hématologie, Boulevard De La Chantourne, Cs 10217, Grenoble Cedex 9
CHU Nancy - Hôpital Brabois
Hématologie, Rue du Morvan, 54511, Vandoeuvre lès Nancy
Centre Hospitalier Universitaire Amiens Picardie
Hématologie clinique, 30 Avenue De La Croix Jourdain, 80054, Amiens Cedex 1
Hopital Saint Louis
Hématologie, 1 Avenue Claude Vellefaux, 75010, Paris
Institut de Cancérologie Lucien Neuwirth
Hématologie, 108 bis avenue Albert Raimond, 42271, Saint Priest en Jarez
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2024-11-05 | 2026-05-27 | 2024-11-05 | 2024-11-05 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 5 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocole 2024-516435-27-00_redacted | 6.1 |
| Recruitment arrangements (for publication) | Document not provided-CPP__2024-516435-27-00 | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 5.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC BUSILVEX | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis French 2024-516435-27-00 | 6.0 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-17 | France | Acceptable 2024-11-05
|
2024-11-05 |