Acute Myeloid LeukaemiaPhase 1/2NCT01422603
Clofarabine Pre-conditioning With Allogeneic Transplant for Acute Myeloid Leukaemia (AML)
A Phase 1/2 study testing Clofarabine in people with Acute Myeloid Leukaemia and Myelodysplasia, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This study has been designed to investigate the safety and feasibility of using a chemotherapy drug, Clofarabine, to reduce the disease burden before a donor transplant, in patients with high risk Acute Myeloid Leukaemia or Myelodysplasia (MDS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukaemia, Myelodysplasia
- What is being tested?
- Clofarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2011to 31 Mar 2015
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cytologically and immunophenotypically (or immunohistochemically) confirmed diagnosis of high risk AML or MDS
- Minimum age of 18 years
- Eligible for allogeneic stem cell transplant by local institutional guidelines
- Suitable matched-related/sibling or volunteer unrelated donor available, as determined by local institutional guidelines
- Negative pregnancy test for females of child-bearing potential within 7 days prior to the start of study treatment
- If sexually active, male and female subjects must agree that they will use an effective method of birth control throughout the active study period
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- Written informed consent
- Capable of and willing to comply with scheduled visits, treatment plan and required laboratory tests
- Adequate renal and hepatic function
Who cannot join
- Psychiatric, addictive or any disorder which compromises ability to give truly informed consent for participation in this study
- Previous Allogeneic Bone Marrow or Peripheral Blood Stem Cell Transplant.
- Pregnant or lactating women. All female subjects of child-bearing potential must have a negative pregnancy test within 7 days prior to the start of treatment.
- Any current active, invasive malignancy excluding AML or MDS
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Wessex Blood and Marrow Transplant Unit, Southampton University Hospitals NHS Trust
Southampton, Hampshire, SO16 6YD
About this study
Official title: A Pilot Study of Clofarabine Pre-conditioning Prior to Full or Reduced Intensity Allogeneic Transplantation in the Treatment of High Risk Acute Myeloid Leukaemia and Myelodysplasia.
This study has been designed to investigate the safety and feasibility of using a chemotherapy drug, Clofarabine, to reduce the disease burden before a donor transplant, in patients with high risk Acute Myeloid Leukaemia or Myelodysplasia (MDS). In this study Clofarabine chemotherapy will be given a few days before a reduced or full intensity donor stem cell transplant and without waiting for normal blood counts to recover. It is hoped that this approach may improve the outcome for patients with high risk AML and MDS after their transplant.
Read the detailed description
This is a pilot study. Twenty patients in total will be treated in two cohorts of 10 patients each.
- Cohort One: Patients suitable for full intensity conditioning will receive Clofarabine pre-conditioning followed by a Cyclophosphamide and Total Body Irradiation conditioned allogeneic stem cell transplant.
- Cohort Two: Patients not suitable for a full intensity TBI-based transplant due to age or co-morbidity will receive Clofarabine pre-conditioning followed by a reduced intensity allogeneic stem cell transplant using Fludarabine, intravenous Busulphan and Campath 1H.
The cohorts will be recruited concurrently. It is anticipated that recruitment of the 20 subjects will be achieved in 18 months to two years.
The study will be conducted at a single centre (Southampton, UK) in the first instance.
This design allows the use of a full intensity, TBI-based transplant conditioning schedule, for younger patients able to tolerate this approach but also the use of a reduced intensity transplant conditioning schedule in older or less fit patients who may still benefit from pre-conditioning with Clofarabine followed by an allogeneic stem cell transplant. This design, therefore, does not restrict potential recruitment to the study on age or performance status alone (within the limits set by ability to tolerate intensive chemotherapy and a transplant procedure).
- Conditions
- Acute Myeloid Leukaemia, Myelodysplasia
- Being tested
- Clofarabine
- Keywords
- High risk, AML, MDS
- Medical subject headings
- Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClofarabineDrug
Clofarabine preconditioning (40mg/m2 daily for 5 days) prior to full intensity allogeneic stem cell transplant
ClofarabineDrug
Clofarabine preconditioning (40mg/m2 daily for 5 days) prior to reduced intensity allogeneic stem cell transplant
| Study group | Role | What they receive |
|---|---|---|
| Clofarabine and Full intensity SCT | Experimental | Cohort One: Patients suitable for full intensity conditioning will receive Clofarabine pre-conditioning followed by a Cyclophosphamide and Total Body Irradiation conditioned allogeneic stem cell transplant (SCT). Receives: Drug: Clofarabine |
| Clofarabine and Reduced intensity SCT | Experimental | Cohort 2: Patients not suitable for a full intensity TBI-based transplant due to age or co-morbidity will receive Clofarabine pre-conditioning followed by a reduced intensity allogeneic stem cell transplant using Fludarabine, intravenous Busulphan and Campath 1H. Receives: Drug: Clofarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment related mortality (TRM)
Treatment related mortality (TRM) measured at day 100 and 1 year post transplant and cause of mortality
Measured: day 100 and 1 year post transplant
Secondary outcomes (9)
Overall survival (OS)
Measured: 1 year post transplant
Event free survival (EFS)
Measured: 1 year post transplant
Efficacy of Clofarabine as a leukaemia bulk-reducing agent prior to transplant conditioning
Efficacy of Clofarabine as a leukaemia bulk-reducing agent prior to transplant conditioning as determined by pre- and post-Clofarabine bone marrow biopsy examination
Measured: Within 4 weeks prior to Clofarabine and 1 to 5 days following Clofarabine
Time to engraftment
Measured: by day 100 post transplant
Donor/recipient chimerism
Measured: day 30, day 100 and 1 year post transplant
Immune reconstitution parameters (T, B and NK cell subsets)
Measured: day 30, day 100 and 1 year post transplant
Duration of hospital stay
Duration of in patient hospital stay for Clofarabine preconditioning chemotherapy and stem cell transplant
Measured: The duration of hospital stay will be measured, an expected average of 7 to 8 weeks
Incidence of acute and chronic graft versus host disease
Measured: 1 year post transplant
Grade of acute and chronic graft versus host disease
Measured: 1 year post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2011 (estimated)
- Study startFeb 2011
- Primary completionMay 2014
- Study completion31 Mar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukaemiaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Southampton NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Deborah S Richardson, MA MB BChir MD FRCP FRCPath, Principal investigator, University Hospital Southampton NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01422603
- Sponsor's protocol ID
- RHM CAN0638
- Other IDs
- 2008-007043-14, 2008
- Status last verified
- Sep 2018
- First submitted
- 22 Aug 2011
- Last updated
- 7 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Clofarabine Pre-conditioning Prior to Full or Reduced Intensity Allogeneic Transplantation in the Treatment of High Risk Acute Myeloid Leukaemia and Myelodysplasia.
- ClinicalTrials.gov ID
- NCT01422603
- Acronym / sponsor ID
- RHM CAN0638
- Conditions
- Acute Myeloid Leukaemia, Myelodysplasia
- Keywords
- High risk, AML, MDS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University Hospital Southampton NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Feb 2011
- Primary completion
- May 2014 (actual)
- Study completion
- 31 Mar 2015 (actual)
- First posted
- 24 Aug 2011 (estimated)
- 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.
This study has been designed to investigate the safety and feasibility of using a chemotherapy drug, Clofarabine, to reduce the disease burden before a donor transplant, in patients with high risk Acute Myeloid Leukaemia or Myelodysplasia (MDS). In this study Clofarabine chemotherapy will be given a few days before a reduced or full intensity donor stem cell transplant and without waiting for normal blood counts to recover. It is hoped that this approach may improve the outcome for patients with high risk AML and MDS after their transplant.
Detailed description
This is a pilot study. Twenty patients in total will be treated in two cohorts of 10 patients each.
- Cohort One: Patients suitable for full intensity conditioning will receive Clofarabine pre-conditioning followed by a Cyclophosphamide and Total Body Irradiation conditioned allogeneic stem cell transplant.
- Cohort Two: Patients not suitable for a full intensity TBI-based transplant due to age or co-morbidity will receive Clofarabine pre-conditioning followed by a reduced intensity allogeneic stem cell transplant using Fludarabine, intravenous Busulphan and Campath 1H.
The cohorts will be recruited concurrently. It is anticipated that recruitment of the 20 subjects will be achieved in 18 months to two years.
The study will be conducted at a single centre (Southampton, UK) in the first instance.
This design allows the use of a full intensity, TBI-based transplant conditioning schedule, for younger patients able to tolerate this approach but also the use of a reduced intensity transplant conditioning schedule in older or less fit patients who may still benefit from pre-conditioning with Clofarabine followed by an allogeneic stem cell transplant. This design, therefore, does not restrict potential recruitment to the study on age or performance status alone (within the limits set by ability to tolerate intensive chemotherapy and a transplant procedure).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clofarabine and Full intensity SCT | Experimental | Drug: ClofarabineCohort One: Patients suitable for full intensity conditioning will receive Clofarabine pre-conditioning followed by a Cyclophosphamide and Total Body Irradiation conditioned allogeneic stem cell transplant (SCT). |
| Clofarabine and Reduced intensity SCT | Experimental | Drug: ClofarabineCohort 2: Patients not suitable for a full intensity TBI-based transplant due to age or co-morbidity will receive Clofarabine pre-conditioning followed by a reduced intensity allogeneic stem cell transplant using Fludarabine, intravenous Busulphan and Campath 1H. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Cytologically and immunophenotypically (or immunohistochemically) confirmed diagnosis of high risk AML or MDS
- Minimum age of 18 years
- Eligible for allogeneic stem cell transplant by local institutional guidelines
- Suitable matched-related/sibling or volunteer unrelated donor available, as determined by local institutional guidelines
- Negative pregnancy test for females of child-bearing potential within 7 days prior to the start of study treatment
Key exclusion criteria (4 listed)
- Psychiatric, addictive or any disorder which compromises ability to give truly informed consent for participation in this study
- Previous Allogeneic Bone Marrow or Peripheral Blood Stem Cell Transplant.
- Pregnant or lactating women. All female subjects of child-bearing potential must have a negative pregnancy test within 7 days prior to the start of treatment.
- Any current active, invasive malignancy excluding AML or MDS
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 |
|---|---|---|
| ClofarabineClofarabine preconditioning (40mg/m2 daily for 5 days) prior to full intensity allogeneic stem cell transplant | Drug | Clofarabine and Full intensity SCT |
| ClofarabineClofarabine preconditioning (40mg/m2 daily for 5 days) prior to reduced intensity allogeneic stem cell transplant | Drug | Clofarabine and Reduced intensity SCT |
Primary outcome
Treatment related mortality (TRM)
Time frame: day 100 and 1 year post transplant
Treatment related mortality (TRM) measured at day 100 and 1 year post transplant and cause of mortality
9 secondary outcomes
Overall survival (OS)
Time frame: 1 year post transplant
Event free survival (EFS)
Time frame: 1 year post transplant
Efficacy of Clofarabine as a leukaemia bulk-reducing agent prior to transplant conditioning
Time frame: Within 4 weeks prior to Clofarabine and 1 to 5 days following Clofarabine
Time to engraftment
Time frame: by day 100 post transplant
Donor/recipient chimerism
Time frame: day 30, day 100 and 1 year post transplant
Immune reconstitution parameters (T, B and NK cell subsets)
Time frame: day 30, day 100 and 1 year post transplant
Duration of hospital stay
Time frame: The duration of hospital stay will be measured, an expected average of 7 to 8 weeks
Incidence of acute and chronic graft versus host disease
Time frame: 1 year post transplant
Grade of acute and chronic graft versus host disease
Time frame: 1 year post transplant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 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.
Deborah S Richardson, MA MB BChir MD FRCP FRCPath principal investigator
University Hospital Southampton NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Clofarabine in people with Acute Myeloid Leukaemia and Myelodysplasia, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.
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 9 inclusion and 4 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: finished, as of the sponsor's last update on 7 Sep 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 United Kingdom. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment related mortality (TRM) (time frame: day 100 and 1 year post transplant). 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 7 Sep 2018.