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

Leukemia, Myeloid, Acute Clinical Trial

— CEREAL  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03235973
• Other study ID #: CEREAL-IPC 2016-010
• Status: Recruiting
• Phase: Phase 1
• Start date: April 28, 2018
• Est. completion date: April 2021

Study information

• Verified date: June 2018
• Source: Institut Paoli-Calmettes
• Contact: Dominique Genre, MD
• Phone: +33491223778
• Email: drci.up[@]ipc.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: April 2021
• Est. primary completion date: April 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoblastic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Drug:
• 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

Locations

Country	Name	City	State
France	Institut Paoli-Calmettes	Marseille	Bouches-du-Rhône

Sponsors (1)

Lead Sponsor	Collaborator
Institut Paoli-Calmettes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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.	30 days after Allo-HSCT
Secondary	Cumulative incidence of acute Graft versus host disease	Cumulative incidence of acute Graft versus host disease according to Gluckberg's classification	100 days
Secondary	Cumulative incidence of chronic Graft versus host disease	Cumulative incidence of chronic Graft versus host disease according to NIH classification	1 year
Secondary	Cumulative incidence of relapse	Cumulative incidence of relapse at 1 year	1 year
Secondary	Cumulative incidence of Non Relapse Mortality	Cumulative incidence of Non Relapse Mortality at day +100 and 1 year after Allo-HSCT	100 days, 1 year