Leukemia, Myeloid, AcutePhase 1CEREALNCT03235973
Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes
A Phase 1 study testing Fludarabine-Cladribine-Busulfan conditioning regimen in people with Leukemia, Myeloid, Acute and Leukemia, Lymphoblastic, Acute, run by Institut Paoli-Calmettes at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Myeloid, Acute, Leukemia, Lymphoblastic, Acute
- What is being tested?
- Fludarabine-Cladribine-Busulfan conditioning regimen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteFrance
- Study dates
- 28 Apr 2018to Apr 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Institut Paoli-Calmettes
Marseille, Bouches-du-Rhône, 13009
Dominique Genre, MD, +33491223778, drci.up@ipc.unicancer.fr
Raynier Devillier, MD,PhD
About this study
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.
- Being tested
- Fludarabine-Cladribine-Busulfan conditioning regimen
- Keywords
- refractory acute leukemia, refractory myelodysplastic syndrome, cladribine dose escalation
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fludarabine-Cladribine-Busulfan conditioning regimenDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine-Cladribine-Busulfan conditioning regimen | Experimental | Not described Receives: Drug: Fludarabine-Cladribine-Busulfan conditioning regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days after Allo-HSCT
Secondary outcomes (4)
Cumulative incidence of acute Graft versus host disease
Cumulative incidence of acute Graft versus host disease according to Gluckberg's classification
Measured: 100 days
Cumulative incidence of chronic Graft versus host disease
Cumulative incidence of chronic Graft versus host disease according to NIH classification
Measured: 1 year
Cumulative incidence of relapse
Cumulative incidence of relapse at 1 year
Measured: 1 year
Cumulative incidence of Non Relapse Mortality
Cumulative incidence of Non Relapse Mortality at day +100 and 1 year after Allo-HSCT
Measured: 100 days, 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2017
- Study start28 Apr 2018
- Primary completionApr 2020 (estimated)
- Study completionApr 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by Institut Paoli-CalmettesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Paoli-Calmettes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Raynier Devillier, MD,PhD, Principal investigator, Institut Paoli-Calmettes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03235973
- Sponsor's protocol ID
- CEREAL-IPC 2016-010
- Acronym
- CEREAL
- Status last verified
- Jun 2018
- First submitted
- 25 Jul 2017
- Last updated
- 28 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT03235973
- Acronym / sponsor ID
- CEREAL / CEREAL-IPC 2016-010
- Keywords
- refractory acute leukemia, refractory myelodysplastic syndrome, cladribine dose escalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Institut Paoli-CalmettesUniversity, hospital or other
- Study start
- 28 Apr 2018 (actual)
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Apr 2021 (estimated)
- First posted
- 1 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fludarabine-Cladribine-Busulfan conditioning regimen | Experimental | Drug: Fludarabine-Cladribine-Busulfan conditioning regimen |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fludarabine-Cladribine-Busulfan conditioning regimenConditioning 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 | Drug | Fludarabine-Cladribine-Busulfan conditioning regimen |
Primary outcome
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)
Time frame: 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.
4 secondary outcomes
Cumulative incidence of acute Graft versus host disease
Time frame: 100 days
Cumulative incidence of chronic Graft versus host disease
Time frame: 1 year
Cumulative incidence of relapse
Time frame: 1 year
Cumulative incidence of Non Relapse Mortality
Time frame: 100 days, 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raynier Devillier, MD,PhD principal investigator
Institut Paoli-Calmettes
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fludarabine-Cladribine-Busulfan conditioning regimen in people with Leukemia, Myeloid, Acute and Leukemia, Lymphoblastic, Acute, run by Institut Paoli-Calmettes at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dominique Genre, MD (+33491223778, drci.up@ipc.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: 30 days after Allo-HSCT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2018.