Condition category
Cancer
Date applied
25/02/2014
Date assigned
25/02/2014
Last edited
17/07/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Mrs Kathryn Wheeler

ORCID ID

Contact details

Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
Viola@trials.bham.ac.uk

Additional identifiers

EudraCT number

2013-002118-11

ClinicalTrials.gov number

Protocol/serial number

15789

Study information

Scientific title

A Phase I trial of combined azactidine and lenalidomide salvage therapy in patients with acute myeloid leukaemia who relapse after allogeneic stem cell transplantation

Acronym

VIOLA

Study hypothesis

Treatment options for patients with acute myeloid leukaemia (AML) who relapse following an allogeneic stem cell transplant (SCT) are extremely limited and most will die of resistant leukaemia. Two drugs, Azacitidine and lenalidomide, have both been shown to have marked clinical activity in patients with AML who have failed to respond to conventional chemotherapy. Of interest, combined treatment with both azacitidine and lenalidomide appears to increase the response rate in patients with AML. Importantly, a number of small studies have demonstrated that both azacitidine and lenalidomide when administered alone can also be clinically active in patients who relapse after a stem cell transplant. To date however, combined treatment with azacitidine and lenalidomide has never been examined in this important patient population. In this study, we plan to determine the best tolerated combined dose of azacitidine and lenalidomide in patients who have relapsed after an allogeneic stem cell transplant. The information produced will inform the design of future clinical trials in patients with AML whose disease has relapsed after an allogeneic transplant. The trial will run in approximately 6 hospitals in the UK. Approximately 27 patients will be recruited to this phase 1 trial.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=15789

Ethics approval

NRES Committee South Central - Oxford B, 21/01/2014, ref. 13/SC/0581

Study design

Non-randomised; Interventional; Design type: Treatment

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 contact your consultant for a patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid)

Intervention

Adverse event discussion, Adverse event discussion 10 minutes. 10 minutes with the doctor (with research nurse if available) within the haematology department; Azacitidine administration, Azacitidine (IMP 1) administration - Azacitidine will be administered by a research nurse/chemotherapy nurse in the haematology department - 20 mins
Bone marrow, A trained doctor will perform bone marrow aspirations on the designated haematology ward/day unit/department - 45 mins.
Discussion and consent, Initial trial discussion and full written informed consent. 1 hour with the doctor (with research nurse if available) within the haematology department; Discussion of GVHD, Discussion of graft versus host disease symptoms 10 minutes with the doctor (with research nurse if available) within the haematology dept
Electrocardiogram (ECG), An ECG will be performed by a research nurse in the haematology/cardiology department - 15 mins

Lenalidomide administration, Lenalidomide (IMP 2) administration - Patients will receive oral capsule(s) of lenalidomide. They will take this medication themselves at home at their convenience; Lenalidomide Education, Lenalidomide Education and Guidance Counselling - 15 mins with the doctor (with research nurse if available) within the haematology department; Medical history, Medical history and demographic data discussion. 30 minutes with the doctor (with research nurse if available) within the haematology department; Patient Diary, Completion of patient diary - Patients will be asked to keep a medication diary from day 10-day 42 of each cycle of therapy (to be completed at the patients convenience).; Physical examination, Physical examination and
vital signs. A doctor will perform a physical exam and a research nurse will
perform and assessment of vital signs in the haematology department - 15 mins; Pregnancy test, Up to 16 pregnancy tests will be required for women of childbearing potential depending on their menstrual pattern. The tests will be performed in the haematology department by a
research nurse - 5 mins; Venepuncture, Venepuncture for haematology and biochemistry assessments. Blood samples will be collected either by a research nurse or
phlebotomist in the haematology department - 5 minutes.; Venepuncture for research, Venepuncture for research
samples - Blood samples for research will be collected by the research - nurse in the haematology department- 5 mins; Follow Up Length: 12 month(s)

Intervention type

Drug

Phase

Phase I

Drug names

azactidine, lenalidomide

Primary outcome measures

Maximum tolerated dose (MTD); Timepoint(s): Maximum tolerated dose (MTD) of lenalidomide in combination with azacitidine in patients with relaps

Secondary outcome measures

1. Best response rate after combined lenalidomide and azacitidine salvage therapy; Timepoint(s): After combined lenalidomide and azacitidine salvage therapy
2. Overall survival; Timepoint(s): Registration - 1yr post trial treatment
3. Tolerability and safety of lenalidomide in combination with azacitidine; Timepoint(s): Each cycle

Overall trial start date

05/02/2014

Overall trial end date

01/02/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with relapsed AML following an alemtuzumab or anti-thymocyte globulin (ATG)-based reduced intensity conditioned allogeneic stem cell transplant using a sibling or unrelated donor
2. Patients able to receive treatment as an outpatient
3. Patients must be willing to comply with the lenalidomide risk management programme
4. Patients must have given written informed consent
5. Patients willing and able to comply with scheduled study visits and laboratory tests

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 30; UK Sample Size: 30

Participant exclusion criteria

1. Patients with active acute or chronic extensive graft-versus-host-disease
(GvHD), or a history of grade 3 or 4 GvHD
2. Patients with hepatic or renal impairment defined as follows:
Total bilirubin ≥ 2.5 x upper limit of normal (ULN)*
Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≥ 3.0 x ULN
Estimated Glomerular Filtration Rate (eGFR) ≤ 40mls/min
*Patients with elevated bilirubin due to Gilbert's syndrome are eligible
3. Patients who have received anti-tumour
therapies, including prior experimental agents or approved anti-tumour
small molecules and biologics, within 28 days before the start of protocol treatment
4. Patients with active symptomatic fungal, bacterial, and/or viral infection
5. Patients with contraindications to receiving azacitidine or lenalidomide
6. Patients with any other condition that in the Investigators opinion would affect the patient's participation in the trial

Recruitment start date

05/02/2014

Recruitment end date

01/02/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cancer Research UK Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Leukaemia & Lymphoma Research (UK); Grant Codes: 13019

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Publication citations

Additional files

Editorial Notes