Clofarabine Pre-conditioning With Allogeneic Transplant for Acute Myeloid Leukaemia (AML)
This study is currently recruiting participants.
Verified August 2011 by University Hospital Southampton NHS Foundation Trust.
Sponsor:
University Hospital Southampton NHS Foundation Trust.
Collaborator:
Genzyme
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
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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
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
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 Leukemia, Myeloid, Acute Leukemia, Myeloid Myelodysplastic Syndromes Preleukemia Neoplasms by Histologic Type Neoplasms |
Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Clofarabine Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 18, 2013