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

NCT01422603 | Completed Phase 1

• 2 other identifiers: RHM CAN06382008-007043-14
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukaemia; Myelodysplasia

Keywords

High risk; AML; MDS

Outcome Measures

Primary Outcomes (1)

• Treatment related mortality (TRM)

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

  day 100 and 1 year post transplant

Secondary Outcomes (9)

• 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

• Time to engraftment

  by day 100 post transplant

• Donor/recipient chimerism

  day 30, day 100 and 1 year post transplant

Study Arms (2)

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).

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.

Drug: Clofarabine

Interventions

Clofarabine DRUG

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

Clofarabine and Full intensity SCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Wessex Blood and Marrow Transplant Unit, Southampton University Hospitals NHS Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts

Interventions

Clofarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Study Officials

• Deborah S Richardson, MA MB BChir MD FRCP FRCPath

  University Hospital Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2011
• First Posted: August 24, 2011
• Study Start: February 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: March 31, 2015
• Last Updated: September 7, 2018

Record last verified: 2018-09

Locations

GB (1)