Clinical trial NCT01422603: Clofarabine Pre-conditioning With Allogeneic Transplant for Acute Myeloid Leukaemia (AML)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukaemia
Myelodysplasia
Keywords: High risk
AML
MDS
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2011-08-24
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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). 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).

Eligibility criteria: Inclusion Criteria:

* 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
* Written informed consent
* Capable of and willing to comply with scheduled visits, treatment plan and required laboratory tests
* Adequate renal and hepatic function

Exclusion Criteria:

* 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

Primary outcomes:
measure: Treatment related mortality (TRM)
timeFrame: day 100 and 1 year post transplant
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 1 year post transplant
measure: Event free survival (EFS)
timeFrame: 1 year post transplant
measure: Efficacy of Clofarabine as a leukaemia bulk-reducing agent prior to transplant conditioning
timeFrame: Within 4 weeks prior to Clofarabine and 1 to 5 days following Clofarabine
measure: Time to engraftment
timeFrame: by day 100 post transplant
measure: Donor/recipient chimerism
timeFrame: day 30, day 100 and 1 year post transplant
measure: Immune reconstitution parameters (T, B and NK cell subsets)
timeFrame: day 30, day 100 and 1 year post transplant
measure: Duration of hospital stay
timeFrame: The duration of hospital stay will be measured, an expected average of 7 to 8 weeks
measure: Incidence of acute and chronic graft versus host disease
timeFrame: 1 year post transplant
measure: Grade of acute and chronic graft versus host disease
timeFrame: 1 year post transplant
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: Wessex Blood and Marrow Transplant Unit, Southampton University Hospitals NHS Trust
state: Hampshire
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Deborah S Richardson, MA MB BChir MD FRCP FRCPath
role: PRINCIPAL_INVESTIGATOR
References: