Back to resultsCladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes (CEREAL)
Primary Purpose
Leukemia, Myeloid, Acute, Leukemia, Lymphoblastic, Acute
Status
Unknown status
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Fludarabine-Cladribine-Busulfan conditioning regimen
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute focused on measuring refractory acute leukemia, refractory myelodysplastic syndrome, cladribine dose escalation
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.
Sites / Locations
- Institut Paoli-CalmettesRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Fludarabine-Cladribine-Busulfan conditioning regimen
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Cumulative incidence of acute Graft versus host disease
Cumulative incidence of acute Graft versus host disease according to Gluckberg's classification
Cumulative incidence of chronic Graft versus host disease
Cumulative incidence of chronic Graft versus host disease according to NIH classification
Cumulative incidence of relapse
Cumulative incidence of relapse at 1 year
Cumulative incidence of Non Relapse Mortality
Cumulative incidence of Non Relapse Mortality at day +100 and 1 year after Allo-HSCT
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03235973
Brief Title
Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes
Acronym
CEREAL
Official Title
Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Unknown status
Study Start Date
April 28, 2018 (Actual)
Primary Completion Date
April 2020 (Anticipated)
Study Completion Date
April 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Paoli-Calmettes
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute, Leukemia, Lymphoblastic, Acute
Keywords
refractory acute leukemia, refractory myelodysplastic syndrome, cladribine dose escalation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Fludarabine-Cladribine-Busulfan conditioning regimen
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Fludarabine-Cladribine-Busulfan conditioning regimen
Intervention Description
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
Primary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
30 days after Allo-HSCT
Secondary Outcome Measure Information:
Title
Cumulative incidence of acute Graft versus host disease
Description
Cumulative incidence of acute Graft versus host disease according to Gluckberg's classification
Time Frame
100 days
Title
Cumulative incidence of chronic Graft versus host disease
Description
Cumulative incidence of chronic Graft versus host disease according to NIH classification
Time Frame
1 year
Title
Cumulative incidence of relapse
Description
Cumulative incidence of relapse at 1 year
Time Frame
1 year
Title
Cumulative incidence of Non Relapse Mortality
Description
Cumulative incidence of Non Relapse Mortality at day +100 and 1 year after Allo-HSCT
Time Frame
100 days, 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dominique Genre, MD
Phone
+33491223778
Email
drci.up@ipc.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Jihane Pakradouni, PharmD, PhD
Phone
+33491223778
Email
drci.up@ipc.unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raynier Devillier, MD,PhD
Organizational Affiliation
Institut Paoli-Calmettes
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Paoli-Calmettes
City
Marseille
State/Province
Bouches-du-Rhône
ZIP/Postal Code
13009
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominique Genre, MD
Phone
+33491223778
Email
drci.up@ipc.unicancer.fr
First Name & Middle Initial & Last Name & Degree
Raynier Devillier, MD,PhD
12. IPD Sharing Statement
Learn more about this trial
Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes
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