Overview

This trial is active, not recruiting.

Conditions acute myeloid leukaemia, myelodysplasia
Treatments clofarabine
Phase phase 1/phase 2
Sponsor University Hospital Southampton NHS Foundation Trust.
Collaborator Genzyme, a Sanofi Company
Start date February 2011
End date May 2014
Trial size 20 participants
Trial identifier NCT01422603, 2008-007043-14, RHM CAN0638

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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).
clofarabine
Clofarabine preconditioning (40mg/m2 daily for 5 days) prior to full intensity allogeneic stem cell transplant
(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.
clofarabine
Clofarabine preconditioning (40mg/m2 daily for 5 days) prior to reduced intensity allogeneic stem cell transplant

Primary Outcomes

Measure
Treatment related mortality (TRM)
time frame: day 100 and 1 year post transplant

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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.
Principal investigator Deborah S Richardson, MA MB BChir MD FRCP FRCPath
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).
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by University Hospital Southampton NHS Foundation Trust..