Clinical trial NCT03235973: Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes
Official title: Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Leukemia, Lymphoblastic, Acute
Keywords: refractory acute leukemia
refractory myelodysplastic syndrome
cladribine dose escalation
Lead sponsor: Institut Paoli-Calmettes
Sponsor class: OTHER
First posted: 2017-08-01
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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)
timeFrame: 30 days after Allo-HSCT
Secondary outcomes:
measure: Cumulative incidence of acute Graft versus host disease
timeFrame: 100 days
measure: Cumulative incidence of chronic Graft versus host disease
timeFrame: 1 year
measure: Cumulative incidence of relapse
timeFrame: 1 year
measure: Cumulative incidence of Non Relapse Mortality
timeFrame: 100 days, 1 year
Other outcomes:
Locations:
city: Marseille
country: France
facility: Institut Paoli-Calmettes
state: Bouches-du-Rhône
Study officials:
affiliation: Institut Paoli-Calmettes
name: Raynier Devillier, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: