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

NCT ID: NCT05917405

Last Updated: 2023-11-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

302 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-14

Study Completion Date

2028-09-14

Brief Summary

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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.

Detailed Description

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Conditions

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Acute Myeloid Leukemia in Remission

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental: CloB2 arm

* 30 mg/m2/day IV clofarabine for 5 days (day-6 to day-2)
* 130 mg/m2/day IV busulfan once daily for 2 days (day -4 and -3)
* ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1) Corticosteroids may be used in profilaxis

Group Type EXPERIMENTAL

Busulfan

Intervention Type DRUG

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

ATG

Intervention Type DRUG

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

Clofarabine

Intervention Type DRUG

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

Comparator: FB2A2 arm

* 30 mg/m2/day IV fludarabine for 5 days (day-6 to day-2)
* 130 mg/m2/day IV busulfan once daily for 2 days (day -4 and -3)
* ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1)

Group Type ACTIVE_COMPARATOR

Fludarabine

Intervention Type DRUG

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

Busulfan

Intervention Type DRUG

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

ATG

Intervention Type DRUG

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

Interventions

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Fludarabine

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

Intervention Type DRUG

Busulfan

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

Intervention Type DRUG

ATG

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

Intervention Type DRUG

Clofarabine

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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%)
* 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
* Women must meet one of the following criteria at the time of inclusion:

* 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.

Exclusion Criteria

* 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%.
* DLCO \<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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nantes University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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patrice CHEVALLIER, Pr

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

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CHU de Nantes

Nantes, Loire Atlantique, France

Site Status RECRUITING

CHU Amiens

Amiens, , France

Site Status NOT_YET_RECRUITING

CHU Angers

Angers, , France

Site Status RECRUITING

CHU Besançon

Besançon, , France

Site Status NOT_YET_RECRUITING

CHU Bordeaux

Bordeaux, , France

Site Status NOT_YET_RECRUITING

CHU Brest

Brest, , France

Site Status RECRUITING

CRLC Caen

Caen, , France

Site Status RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, , France

Site Status NOT_YET_RECRUITING

APHP Créteil

Créteil, , France

Site Status NOT_YET_RECRUITING

CHU Grenoble

Grenoble, , France

Site Status RECRUITING

CHRU Lille

Lille, , France

Site Status NOT_YET_RECRUITING

CHU Limoges

Limoges, , France

Site Status NOT_YET_RECRUITING

CHU Lyon

Lyon, , France

Site Status NOT_YET_RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status NOT_YET_RECRUITING

CHU Montpellier

Montpellier, , France

Site Status RECRUITING

CHRU Nancy

Nancy, , France

Site Status NOT_YET_RECRUITING

CHU Paris St-Louis

Paris, , France

Site Status NOT_YET_RECRUITING

Pitie-Salpetriere, APHP

Paris, , France

Site Status NOT_YET_RECRUITING

St-Antoine, APHP

Paris, , France

Site Status NOT_YET_RECRUITING

CHU Poitiers

Poitiers, , France

Site Status NOT_YET_RECRUITING

CHU Rennes

Rennes, , France

Site Status NOT_YET_RECRUITING

CHU St-Etienne

Saint-Etienne, , France

Site Status NOT_YET_RECRUITING

CRLC Toulouse

Toulouse, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Patrice CHEVALLIER, Pr

Role: CONTACT

MARION GAUTIER

Role: CONTACT

+33253526204

Facility Contacts

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Patrice Chevallier, Pr

Role: primary

0240083271

Amandine CHARBONNIER, Dr

Role: primary

0322455606

Sylvie FRANCOIS, Dr

Role: primary

0241354472

Ana BERCEANU, Dr

Role: primary

0381668232

Edouard FORCADE, Dr

Role: primary

0557656511

Gaelle GUILLERM, Dr

Role: primary

0298223395

Sylvain CHANTEPIE, Dr

Role: primary

0231272073

Jacques-Olivier BAY, Pr

Role: primary

0473750750

Sebastien MAURY, Pr

Role: primary

0149812059

Martin CARRE, Dr

Role: primary

0476769445

Valérie COITEUX, Dr

Role: primary

0320445551

Pascal TURLURE, Dr

Role: primary

0555056642

Helene LABUSSIERE-WALLET, Dr

Role: primary

0472117402

Raynier DEVILLIER, Dr

Role: primary

0491223868

Patrice CEBALLOS, Dr

Role: primary

0467338079

Marie-Therese RUBIO, Pr

Role: primary

0383153030

Marie ROBIN, Dr

Role: primary

0142499639

Stéphanie NGUYEN, Pr

Role: primary

0142162823

Mohamad MOHTY, Pr

Role: primary

0149282620

Natacha MAILLARD, Dr

Role: primary

0549444472

Jean-Baptiste MEAR, Dr

Role: primary

0299284291

Jerome CORNILLON, Dr

Role: primary

0477917000

Anne HUYNH, Dr

Role: primary

0531155527

Other Identifiers

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RC22_0524

Identifier Type: -

Identifier Source: org_study_id

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