Clofarabine Pre-conditioning With Allogeneic Transplant for Acute Myeloid Leukaemia (AML)

Sponsor

University Hospital Southampton NHS Foundation Trust (Other)

Overall Status

Completed

CT.gov ID

NCT01422603

Collaborator

Genzyme, a Sanofi Company (Industry)

Enrollment

Location

Arms

49.9

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukaemia Myelodysplasia	Drug: Clofarabine Drug: Clofarabine	Phase 1/Phase 2

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

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Feb 1, 2011

Actual Primary Completion Date :

May 1, 2014

Actual Study Completion Date :

Mar 31, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clofarabine and Full intensity SCT 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).	Drug: Clofarabine Clofarabine preconditioning (40mg/m2 daily for 5 days) prior to full intensity allogeneic stem cell transplant
Experimental: Clofarabine and Reduced intensity SCT 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.	Drug: Clofarabine Clofarabine preconditioning (40mg/m2 daily for 5 days) prior to reduced intensity allogeneic stem cell transplant

Arm

Intervention/Treatment

Experimental: Clofarabine and Full intensity SCT

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).

Drug: Clofarabine

Clofarabine preconditioning (40mg/m2 daily for 5 days) prior to full intensity allogeneic stem cell transplant

Experimental: Clofarabine and Reduced intensity SCT

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.

Drug: Clofarabine

Clofarabine preconditioning (40mg/m2 daily for 5 days) prior to reduced intensity allogeneic stem cell transplant

Outcome Measures

Primary Outcome Measures

Treatment related mortality (TRM) [day 100 and 1 year post transplant]
Treatment related mortality (TRM) measured at day 100 and 1 year post transplant and cause of mortality

Secondary Outcome Measures

Overall survival (OS) [1 year post transplant]
Event free survival (EFS) [1 year post transplant]
Efficacy of Clofarabine as a leukaemia bulk-reducing agent prior to transplant conditioning [Within 4 weeks prior to Clofarabine and 1 to 5 days following Clofarabine]
Efficacy of Clofarabine as a leukaemia bulk-reducing agent prior to transplant conditioning as determined by pre- and post-Clofarabine bone marrow biopsy examination
Time to engraftment [by day 100 post transplant]
Donor/recipient chimerism [day 30, day 100 and 1 year post transplant]
Immune reconstitution parameters (T, B and NK cell subsets) [day 30, day 100 and 1 year post transplant]
Duration of hospital stay [The duration of hospital stay will be measured, an expected average of 7 to 8 weeks]
Duration of in patient hospital stay for Clofarabine preconditioning chemotherapy and stem cell transplant
Incidence of acute and chronic graft versus host disease [1 year post transplant]
Grade of acute and chronic graft versus host disease [1 year post transplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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