Pilot safety/tolerability study of Lenalidomide administered as monotherapy and in combination with standard chemotherapy for Acute Myeloid Leukaemia/high-risk myelodysplastic syndrome with structural abnormalities of chromosome 5

ISRCTN	ISRCTN58492795
DOI	https://doi.org/10.1186/ISRCTN58492795
Secondary identifying numbers	HM08/8451

Submission date: 18/06/2008
Registration date: 11/07/2008
Last edited: 25/10/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/A-study-lenalidomide-acute-myeloid-leukaemia-high-risk-myelodysplastic-syndrome-abnormality-chromosome-5

Contact information

Prof David Bowen
Scientific

Consultant Haematologist
Bexley Wing 3rd Floor
St James's Institute of Oncology
Beckett Street
Leeds
LS9 7DF
United Kingdom

Study information

Study design	Late phase II three-outcome non-randomised design
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Pilot safety/tolerability study of Lenalidomide administered as monotherapy and in combination with standard chemotherapy for Acute Myeloid Leukaemia/high-risk myelodysplastic syndrome with structural abnormalities of chromosome 5
Study acronym	AML Len5
Study objectives	The primary objective is to assess safety and tolerability of the combination of oral lenalidomide administered as a single agent and simultaneously with induction chemotherapy using cytosine arabinoside, daunorubicin +/- etoposide (ADE) for patients with acute myeloid leukaemia/high-risk myelodysplastic syndrome (AML/MDS) and chromosome 5 cytogenetic abnormalities.
Ethics approval(s)	Ethics approval to be submitted during summer 2008. The MREC committee will be assigned by NRES.
Health condition(s) or problem(s) studied	Acute myeloid leukaemia, high-risk myelodysplastic syndrome, chromosome 5 cytogenetic abnormalities
Intervention	For patients with greater than 5% blasts at trial entry: Lenalidomide monotherapy: Lenalidomide will be administered orally at 10 mg daily for 21 days. Bone marrow examination will be performed at day 28. If complete remission (CR) has been achieved, consolidation with lenalidomide plus ADE 3+8+5 should follow. If less than 50% blast reduction (NR), proceed to induction with lenalidomide plus ADE 3+10+5. If no CR but blasts have reduced by greater than 50% from baseline (BMR), lenalidomide will be restarted as soon after day 28 as possible for a further 21 days. Bone marrow examination will then be performed at day 56 (or day 28 of cycle 2). If CR has been achieved, consolidation with lenalidomide plus ADE 3+8+5 will be given. If no CR, proceed to induction with lenalidomide plus ADE 3+10+5. Patients with progressive disease during monotherapy will proceed immediately to induction with lenalidomide plus ADE 3+10+5. Induction: lenalidomide plus ADE 3+10+5 Lenalidomide will be administered orally at 10 mg daily for 10 days concurrently with ADE induction therapy (3+10+5) which comprises: 1. Cytosine arabinoside 100 mg/m^2 twice daily by intravenous push for 10 days 2. Daunorubicin 50 mg/m^2 days 1, 3, 5 by intravenous infusion 3. Etoposide 100 mg/m^2 daily days 1 - 5 by intravenous infusion Consolidation: Consolidation will be given after achievement of CR with either lenalidomide monotherapy or following induction with lenalidomide plus ADE. Consolidation will also be administered to patients achieving partial remission (PR) with lenalidomide plus ADE induction. Consolidation will comprise lenalidomide plus ADE 3+8+5. Consolidation should only be commenced after haematopoietic recovery, defined as neutrophils greater than 1 x 10^9/l and platelets greater than 80 x 10^9/l. Lenalidomide will be administered orally at 10 mg daily for 10 days concurrently with course 2 of ADE (3+8+5), which comprises: 1. Cytosine arabinoside 100 mg/m^2 twice daily by intravenous push for 8 days 2. Daunorubicin 50 mg/m^2 days 1, 3, 5 by intravenous infusion 3. Etoposide 100 mg/m^2 daily days 1 - 5 by intravenous infusion For patients with less than 5% blasts at trial entry (Int-2 MDS): Lenalidomide monotherapy: Lenalidomide will be administered orally at 10 mg daily for 21 days. Bone marrow examination will be performed at day 28. If CR or PR has been achieved, a second course of oral lenalidomide 10 mg daily for a further 21 days will be administered. For patients in CR, await haematopoietic recovery before the second course of lenalidomide defined as platelets greater than 80 x 10^9/l and neutrophils greater than 1 x 10^9/l. For patients in PR recommence lenalidomide on day 28. Patients in CR after course 1 or 2 should receive one additional course of lenalidomide 10 mg daily orally for 21 days after documentation of CR. Such patients are then eligible for allogeneic stem cell transplant subject to donor availability. If no transplant option, patients should commence maintenance lenalidomide for 12 months. Post-remission therapy will be at the discretion of the investigator. All patients considered eligible for allogeneic stem cell transplantation and with a suitable donor should be offered a transplant. Maintenance: Lenalidomide after post-remission therapy for non-transplant candidates - 10 mg daily x 21 days repeated monthly for a maximum of 12 months (venous thromboembolism [VTE] prophylaxis will be considered on a case by case basis).
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Lenalidomide, cytosine arabinoside, daunorubicin, etoposide
Primary outcome measure	The primary endpoint of this study is safety and tolerability of the combination therapy, assessed by two outcomes: early death rate and the proportion of patients recovering their platelets and surviving by 42 days after chemotherapy. If the treatment is found to be safe and tolerable for BOTH of these endpoints, then we will consider the short term efficacy in terms of complete remission rate as a third primary endpoint and we will use this to determine whether or not to proceed to a phase III trial. The early death rate and proportion of patients recovering platelets and surviving will be assessed at four points throughout the trial; after 10 patients, 19 patients, 30 patients, and 39 patients have been recruited.
Secondary outcome measures	1. Time to recovery of neutrophils 2. Blood product usage 3. Length of time spent in hospital
Overall study start date	01/01/2009
Completion date	31/12/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	39
Total final enrolment	14
Key inclusion criteria	1. Patients diagnosed with primary/relapsed/refractory AML (as defined by World Health Organization [WHO]) or high risk MDS (defined as International Prognostic Scoring System [IPSS] Int-2/High) with chromosome 5 cytogenetic abnormalities 2. Aged 18 years old, either sex 3. Considered suitable for intensive chemotherapy 4. Capable of understanding and complying with protocol requirements 5. Written informed consent
Key exclusion criteria	1. Use of prior investigational agents within four weeks 2. The subject has received lenalidomide in a previous clinical study or as a therapeutic agent 3. The subject has a history or clinical manifestations of human immunodeficiency virus (HIV) or other active infection 4. The subject has a history of hypersensitivity or allergies to lactose 5. If female, the subject is pregnant or lactating 6. The subject has another active malignancy 7. The subject has other severe concurrent disease or mental illness 8. Eastern Cooperative Oncology Group (ECOG) performance status greater than 2 9. Myocardial dysfunction (as defined by left ventricular ejection fraction less than 50%) 10. Creatinine clearance (Cockroft) less than 60 mls/min 11. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) greater than 3 x upper limit of normal (ULN)
Date of first enrolment	01/01/2009
Date of final enrolment	31/12/2009

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

St James's Institute of Oncology

Leeds
LS9 7DF
United Kingdom

Sponsor information

Leeds Teaching Hospitals NHS Trust (UK)
Hospital/treatment centre

c/o Dr Derek Norfolk
Associate Director of R&D
Department of Research & Development
A/B Floor, Old Site Worsley Building
Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
England
United Kingdom

Website	http://www.leedsth.nhs.uk/
"ROR"	https://ror.org/00v4dac24

Funders

Funder type

Industry

Cancer Research UK (CRUK) (UK) (ref: C24417/A10075) - funded by a grant from the Feasibility Study Committee (FSC)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Celgene Ltd (UK) (ref: RV-AML-NCRI-179)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	28/08/2013		Yes	No
Plain English results			25/10/2022	No	Yes

Editorial Notes

25/10/2022: Cancer Research UK plain English results link and total final enrolment added.