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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by University Hospital Southampton NHS Foundation Trust..
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier:
NCT01422603
First received: August 22, 2011
Last updated: August 24, 2011
Last verified: August 2011
  Purpose

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 Intervention Phase
Acute Myeloid Leukaemia
Myelodysplasia
Drug: Clofarabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by University Hospital Southampton NHS Foundation Trust.:

Primary Outcome Measures:
  • Treatment related mortality (TRM) [ Time Frame: day 100 and 1 year post transplant ] [ Designated as safety issue: Yes ]
    Treatment related mortality (TRM) measured at day 100 and 1 year post transplant and cause of mortality


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: 1 year post transplant ] [ Designated as safety issue: No ]
  • Event free survival (EFS) [ Time Frame: 1 year post transplant ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: by day 100 post transplant ] [ Designated as safety issue: Yes ]
  • Donor/recipient chimerism [ Time Frame: day 30, day 100 and 1 year post transplant ] [ Designated as safety issue: No ]
  • Immune reconstitution parameters (T, B and NK cell subsets) [ Time Frame: day 30, day 100 and 1 year post transplant ] [ Designated as safety issue: No ]
  • Duration of hospital stay [ Time Frame: The duration of hospital stay will be measured, an expected average of 7 to 8 weeks ] [ Designated as safety issue: Yes ]
    Duration of in patient hospital stay for Clofarabine preconditioning chemotherapy and stem cell transplant

  • Incidence of acute and chronic graft versus host disease [ Time Frame: 1 year post transplant ] [ Designated as safety issue: Yes ]
  • Grade of acute and chronic graft versus host disease [ Time Frame: 1 year post transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: February 2011
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01422603

Contacts
Contact: Deborah S Richardson, MA MB BChir MD FRCP FRCPath +44 2380 777222 ext 6164 dsr@soton.ac.uk
Contact: Kim H Orchard, MB BS PhD FRCP FRCPath +44 2380 777222 ext 4118 kho@soton.ac.uk

Locations
United Kingdom
Wessex Blood and Marrow Transplant Unit, Southampton University Hospitals NHS Trust Recruiting
Southampton, Hampshire, United Kingdom, SO16 6YD
Contact: Deborah S Richardson, MA MB BChir MD FRCP FRCPath    +44 2380 777222 ext 6164    dsr@soton.ac.uk   
Principal Investigator: Deborah S Richardson, MA MB BChir MD FRCP FRCPath         
Sub-Investigator: Kim H Orchard, MB BS PhD FRCP FRCPath         
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust.
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Deborah S Richardson, MA MB BChir MD FRCP FRCPath University Hospital Southampton NHS Foundation Trust.
  More Information

No publications provided

Responsible Party: University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier: NCT01422603     History of Changes
Other Study ID Numbers: RHM CAN0638, 2008-007043-14
Study First Received: August 22, 2011
Last Updated: August 24, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University Hospital Southampton NHS Foundation Trust.:
High risk
AML
MDS

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Clofarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014