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

Phase 1

• Conditions: Leukemia, Myeloid, Acute; Leukemia, Lymphoblastic, Acute
• Interventions: Drug: Fludarabine-Cladribine-Busulfan conditioning regimen

• Registration Number: NCT03235973
• Lead Sponsor: Institut Paoli-Calmettes

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-07-25
• Study First Submitted QC: 2017-07-31
• Study First Posted: 2017-08-01
• Study Start: 2018-04-28
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-26
• Last Update Posted: 2018-06-28
• Primary Completion: 2020-04
• Study Completion: 2021-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 29

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fludarabine-Cladribine-Busulfan conditioning regimen	Fludarabine-Cladribine-Busulfan conditioning regimen	-

Primary Outcome Measures

Name	Time	Method
estimation of the maximal tolerable dose,if any,and recommended phase II dose of cladribine administered as in combination with fludarabine and PK-guided IV busulfan prior Allo-HSCT for refractory acute leukemia and myelodysplastic syndrome (MDS)	30 days after Allo-HSCT	Occurrence ratio of dose-limiting toxicity defined as any grade ≥ 3 toxicity according to CTCAE (version 4.03 ) attributable to conditioning regimen (extra-medullary toxicity), considered to be related or probably related to the Cla-Fu-Bu RTC by the investigator.

Secondary Outcome Measures

Name	Time	Method
Cumulative incidence of acute Graft versus host disease	100 days	Cumulative incidence of acute Graft versus host disease according to Gluckberg's classification
Cumulative incidence of chronic Graft versus host disease	1 year	Cumulative incidence of chronic Graft versus host disease according to NIH classification
Cumulative incidence of relapse	1 year	Cumulative incidence of relapse at 1 year
Cumulative incidence of Non Relapse Mortality	100 days, 1 year	Cumulative incidence of Non Relapse Mortality at day +100 and 1 year after Allo-HSCT

Trial Locations

Locations (1)

Institut Paoli-Calmettes; 🇫🇷 Marseille, Bouches-du-Rhône, France