Condition category
Cancer
Date applied
13/02/2008
Date assigned
20/03/2008
Last edited
17/01/2012
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Charles Craddock

ORCID ID

Contact details

Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
+44 (0)121 627 5824
charles.craddock@uhb.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RG 07-187

Study information

Scientific title

Phase ll study of the adjunctive use of azacitidine in patients undergoing reduced intensity allogeneic transplantation in acute myeloid leukaemia and myelodysplasia

Acronym

RICAZA

Study hypothesis

Disease relapse is the major cause of treatment failure after allogeneic transplantation using reduced intensity conditioning (RIC) regimens in patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) and therefore strategies which reduce the risk of disease relapse are required. Although there has been interest in the use of prophylactic donor lymphocyte infusions (DLI) to reduce the risk of relapse, their use is associated with a significant risk of severe graft-versus-host disease (GVHD) when administered early post-transplant. Azacitidine has potent activity against malignant myeloid progenitors and this study aims to examine whether its administration post-transplant can modify the kinetics of disease relapse after a RIC allograft for AML or MDS thereby postponing or eliminating the requirement for DLI.

Ethics approval

West Midlands Research Ethics Committee on 24/04/2008 (ref: 08/H1208/4)

Study design

Phase II, multicentre, single arm, open-label, non-randomised study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Acute myeloid leukaemia (AML) or myelodysplasia (MDS)

Intervention

All participants will receive azacitidine administered six weeks after undergoing reduced intensity conditioned allogeneic transplantation. Azacitidine will be administered subcutaneously for 5 days for 10 cycles (each cycle being 28 days) at a dose of 36 mg/m^2.

Total duration of trial treatment: 11 months; follow up period: 24 months.

Intervention type

Drug

Phase

Phase II

Drug names

Azacitidine

Primary outcome measures

Safety of azacitidine treatment. Adverse events and therapy-related side effects will be monitored continuously during azacitidine treatment and until 28 days after the last dose.

Secondary outcome measures

1. Relapse rate, assessed at 12 months post-transplant
2. Survival, assessed annually until 3 years post-transplant

Overall trial start date

01/06/2008

Overall trial end date

31/05/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients (male and female) between the age of 18 - 65 years in whom allogeneic transplantation using a myeloablative conditioning regimen is contra-indicated
2. Patients who fulfill the World Health Organization (WHO) criteria for AML or MDS
3. Patients with a human leukocyte antigen (HLA) identical sibling or suitable matched unrelated donor
4. Must give written informed consent and be able to comply with the protocol for the duration of the study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40 patients

Participant exclusion criteria

1. Patients with contra-indications to receiving fludarabine or azacitidine
2. Pregnant or lactating women or adults of reproductive potential not willing to use appropriate medically approved contraception during the trial and for 12 months post-azacitidine
3. Any co-morbidity that in the investigators opinion will affect the patients participation in this study

Recruitment start date

01/06/2008

Recruitment end date

31/05/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Centre for Clinical Haematology
Birmingham
B15 2TH
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Research and Commercial Services
Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

http://www.rcs.bham.ac.uk

Funders

Funder type

Industry

Funder name

Pharmion (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

University of Birmingham (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22234690

Publication citations

  1. Results

    Goodyear OC, Dennis M, Jilani NY, Loke J, Siddique S, Ryan G, Nunnick J, Khanum R, Raghavan M, Cook M, Snowden JA, Griffiths M, Russell N, Yin J, Crawley C, Cook G, Vyas P, Moss P, Malladi R, Craddock CF, Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML)., Blood, 2012, 119, 14, 3361-3369, doi: 10.1182/blood-2011-09-377044.

Additional files

Editorial Notes