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

NCT ID: NCT03235973

Last Updated: 2018-06-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-28
• Study Completion Date: 2021-04-30

Brief Summary

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.

Conditions

Leukemia, Myeloid, Acute; Leukemia, Lymphoblastic, Acute

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fludarabine-Cladribine-Busulfan conditioning regimen

Group Type: EXPERIMENTAL

Fludarabine-Cladribine-Busulfan conditioning regimen

Intervention Type: DRUG

Conditioning regimen will be performed from day -6 to day -2 and contains:

• Fludarabine 10 mg/m²/d during 5 days (day-6 to day-2).
• Cladribine during 5 days (day-6 to day-2) at one the following define dose level:

• Dose 1: 10 mg/m²/d
• Dose 2: 15 mg/m²/d
• Dose 3: 20 mg/m²/d
• Dose 4: 25 mg/m²/d
• IV busulfan will be given on day-6 using fixed dose as following:

• If age ≤ 60 years: starting dose of 130 mg/m²
• If age > 60 years: starting dose of 100 mg/m² No busulfan will be administered at day-5, allowing the pharmacokinetic (PK) analyses . Subsequent infusion of IV busulfan will be performed from day-4 to day-2 at the dose recommended by PK analyses

Interventions

Fludarabine-Cladribine-Busulfan conditioning regimen

Conditioning regimen will be performed from day -6 to day -2 and contains:

• Fludarabine 10 mg/m²/d during 5 days (day-6 to day-2).
• Cladribine during 5 days (day-6 to day-2) at one the following define dose level:

• Dose 1: 10 mg/m²/d
• Dose 2: 15 mg/m²/d
• Dose 3: 20 mg/m²/d
• Dose 4: 25 mg/m²/d
• IV busulfan will be given on day-6 using fixed dose as following:

• If age ≤ 60 years: starting dose of 130 mg/m²
• If age > 60 years: starting dose of 100 mg/m² No busulfan will be administered at day-5, allowing the pharmacokinetic (PK) analyses . Subsequent infusion of IV busulfan will be performed from day-4 to day-2 at the dose recommended by PK analyses

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut Paoli-Calmettes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raynier Devillier, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli-Calmettes

Locations

Institut Paoli-Calmettes

Marseille, Bouches-du-Rhône, France

Site Status: RECRUITING

Countries

France

Central Contacts

Dominique Genre, MD

Role: CONTACT

drci.up@ipc.unicancer.fr

+33491223778

Jihane Pakradouni, PharmD, PhD

Role: CONTACT

drci.up@ipc.unicancer.fr

+33491223778

Facility Contacts

Dominique Genre, MD

Role: primary

drci.up@ipc.unicancer.fr

+33491223778

Other Identifiers

CEREAL-IPC 2016-010

Identifier Type: -

Identifier Source: org_study_id