Study Comparing the Efficacy of 2 RIC Regimens (Clofarabine vs Fludarabine) in Adults With AML Eligible to Allo-SCT

NCT05917405 | Recruiting Phase 2 DMC

• 1 other identifier: RC22_0524
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 23

Brief Summary

Relapse remains the main cause of death in patients with myeloid malignancies, especially after an allotransplant. Using drugs with higher anti-leukemic activity as part of the conditioning regimen is one of the strategies to decrease relapse incidence in this population. Retrospective studies have shown that clofarabine can achieve impressive results compared to the use of fludarabine in acute myeloid leukemia (AML) as part of the conditioning regimen. Confirming such results in a prospective manner would definitely establish the CloB2A2 as a superior reduced-intensity conditioning (RIC) regimen compared to the FB2A2 for AML patients.302 AML patients (151 in each arm) in complete remission at transplant will be included with the main objective to demonstrate a significant better 2-year overall survival for CloB2A2 cases (70% vs 55%). A cost-utility analysis and a cost-effectiveness analysis will be also performed as well as an assessment of the quality of life after transplant. Clofarabine will be furnished to all centers. The duration of the study will be 5 years with 3 years of inclusion and 2 years of follow-up for each patient.

Conditions

Acute Myeloid Leukemia in Remission

Keywords

Acute Myeloid Leukemia; Clofarabine; fludarabine; reduced intensity conditioning regimen; allogeneic stem cells transplantation

Outcome Measures

Primary Outcomes (1)

• To compare 2-year OS between patients with AML in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT.

  OS is defined as the time from day 1 of conditioning to death or last follow-up for survivors.

  2 years

Secondary Outcomes (23)

• To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT: Engraftment, primary and secondary graft failure

  day +30/42 and 2 years

• To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT: Neutrophils and platelet recoveries

  2 years

• To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT: 2-year DFS

  2 years

• To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT:-2-year relapse incidence

  2 years

• To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT:2-year NRM

  2 years

Study Arms (2)

Experimental: CloB2 arm

EXPERIMENTAL

* 30 mg/m2/day IV clofarabine for 5 days (day-6 to day-2) * 3.2mg/kg/day IV busulfan once daily for 2 days (day -5 and -4) * ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1) Corticosteroids may be used in profilaxis

Drug: Busulfan; Drug: ATG; Drug: Clofarabine

Comparator: FB2A2 arm

ACTIVE COMPARATOR

* 30 mg/m2/day IV fludarabine for 5 days (day-6 to day-2) * 3.2 mg/kg/day IV busulfan once daily for 2 days (day -5 and -4) * ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1)

Drug: Fludarabine; Drug: Busulfan; Drug: ATG

Interventions

Fludarabine DRUG

30 mg/m2/day IV fludarabine for 5 days (day-6 to day-2)

Comparator: FB2A2 arm

Busulfan DRUG

130 mg/m2/day IV busulfan once daily for 2 days (day -4 and -3)

Comparator: FB2A2 arm; Experimental: CloB2 arm

ATG DRUG

Thymoglobuline®: 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1)

Comparator: FB2A2 arm; Experimental: CloB2 arm

Clofarabine DRUG

30 mg/m2/day IV clofarabine for 5 days (day-6 to day-2)

Experimental: CloB2 arm

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years' old
• De novo or secondary AML (according to ELN 2022 classification) in complete cytological remission at time of transplant (bone marrow blast count \< 5%) or MDS/LAM with bone marrow blast count ≤ 5%
• Patients in first or second line therapy are allowed
• Patient eligible to a RIC regimen : patients aged ≥ 60 year old or \<60 with co-morbidity(ies).
• Patient with a related or an unrelated matched donor
• Graft using only peripheral blood stem cells
• Performance status ECOG 0 - 2
• Who provide their written informed consent
• Previous allograft allowed
• Affiliated with French social security system or beneficiary from such system
• use adequate contraceptive measures as recommended by the CTFG (Recommendations related to contraception and pregnancy testing in clinical trials v1.1; includes injectable implants, dual hormone birth control pills, intrauterine devices, abstinence from sex, or a sterilized partner), and have a negative pregnancy test (urine or serum pregnancy test) prior to receiving the first dose of study drug;
• or be post-menopausal (over 50 years of age with amenorrhea for at least 12 months after discontinuation of all exogenous hormonal therapy)
• or (if under 50 years of age) have been amenorrheic for at least 12 months after discontinuation of exogenous hormonal therapy and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels corresponding to post-menopausal levels
• or have undergone irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (this operation must be documented).
• Contraception methods must be prescribed using effective contraceptive methods during treatment and within 6 months for women of childbearing age (WOCB) and 6 months for men in case they have sexual relations with WOCB after the last dose of Fludarabine/Clofarabine.

You may not qualify if:

• Pro-myelocytic leukemia
• Patient eligible to a myeloablative conditioning regimen
• Patient with haploidentical, mismatched unrelated donor or umbilical cord blood
• Pregnant or breastfeeding woman or patient refusing contraceptive mesures
• HIV positive
• Active Hepatitis B or C
• Left ventricular ejection fraction \< 50%.
• DLCOc \<40%
• Uncontrolled infection
• Uncontrolled haemolytic anaemia
• Creatinine clearance \< 50 ml/min (evaluated by MDRD or CKDEPI).
• Serum bilirubine \> 30 mmol/l, Cytolysis \> 5 the upper limit range
• Previous or concurrent second malignancy except for adequately treated basal cell carcinoma of the skin, curatively treated in situ carcinoma of the cervix, curatively treated solid cancer, with no evidence of disease for at least 2 years
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Participation to another interventional study during the last month or expected participation to another interventional study during participation to the FLUCLORIC study.

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (23)

CHU de Nantes

Nantes, Loire Atlantique, 44000, France

RECRUITING

CHU Amiens

Amiens, France

RECRUITING

CHU Angers

Angers, France

RECRUITING

CHU Besançon

Besançon, France

RECRUITING

CHU Bordeaux

Bordeaux, France

NOT YET RECRUITING

CHU Brest

Brest, France

RECRUITING

CRLC Caen

Caen, France

RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, France

RECRUITING

APHP Créteil

Créteil, France

RECRUITING

CHU Grenoble

Grenoble, France

RECRUITING

CHRU Lille

Lille, France

NOT YET RECRUITING

CHU Limoges

Limoges, France

RECRUITING

CHU Lyon

Lyon, France

RECRUITING

Institut Paoli Calmettes

Marseille, France

RECRUITING

CHU Montpellier

Montpellier, France

RECRUITING

CHRU Nancy

Nancy, France

RECRUITING

CHU Paris St-Louis

Paris, France

RECRUITING

Pitie-Salpetriere, APHP

Paris, France

RECRUITING

St-Antoine, APHP

Paris, France

RECRUITING

CHU Poitiers

Poitiers, France

NOT YET RECRUITING

CHU Rennes

Rennes, France

RECRUITING

CHU St-Etienne

Saint-Etienne, France

RECRUITING

CRLC Toulouse

Toulouse, France

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

fludarabine; Busulfan; Clofarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Study Officials

• patrice CHEVALLIER, Pr

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrice CHEVALLIER, Pr

CONTACT

patrice.chevallier@chu-nantes.fr

MARION GAUTIER

CONTACT

+33253526204; marion.gautier@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2023
• First Posted: June 23, 2023
• Study Start: September 14, 2023
• Primary Completion (Estimated): September 14, 2028
• Study Completion (Estimated): September 14, 2028
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (23)