Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes (CEREAL)

Institut Paoli-Calmettes

Status and phase: Unknown; Phase 1

Conditions: Leukemia, Lymphoblastic, Acute; Leukemia, Myeloid, Acute

Treatments: Drug: Fludarabine-Cladribine-Busulfan conditioning regimen

Study type: Interventional

Funder types: Other

Identifiers

NCT03235973

CEREAL-IPC 2016-010

Details and patient eligibility

About

The investigators focused on patients with refractory acute leukemia or MDS and designed a phase 1 trial of escalated cladribine doses in the Cla-Flu-Bu RTC regimen using PK-guided myeloablative busulfan doses. This scheme allows combining different optimization of RTC experienced over years (Flu-Bu RTC, PK-guided myeloablative busulfan doses, a second purine analog cladribine) to approach a specific platform to treat refractory diseases.

Enrollment: 29 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18-70
• ECOG 0 or 1
• Acute leukemia (AML or ALL) without criteria for CR or high risk MDS without criteria for CR
• Availability of a donor among following oHLA identical sibling oHaploidentical donor o10/10 or 9/10 allele-level HLA matched unrelated donor
• Signed informed consent
• Patient affiliated to the national "Social Security" regimen or beneficiary of this regimen

Exclusion criteria

• Contraindication for Allo-HSCT
• Cord blood Allo-HSCT
• Current active disease or positive serology for HIV, and/or HCV with detectable viremia and/ or HBV with positive Hbs Antigen.
• Renal failure with creatinine clearance < 30 ml/ min
• Decompensated haemolytic anaemia
• Hypersensitivity to an active substance or to any of the excipients
• Acute urinary infection
• Pre-existing haemorrhagic cystitis
• Woman of childbearing potential not using an effective contraception .
• Pregnant or lactating women
• Any serious concurrent uncontrolled medical disorder
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Fludarabine-Cladribine-Busulfan conditioning regimen

Experimental group

Treatment:

Drug: Fludarabine-Cladribine-Busulfan conditioning regimen