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
Protocol serial number HM08/8451
Sponsor Leeds Teaching Hospitals NHS Trust (UK)
Funders Cancer Research UK (CRUK) (UK) (ref: C24417/A10075) - funded by a grant from the Feasibility Study Committee (FSC), Celgene Ltd (UK) (ref: RV-AML-NCRI-179)
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

Primary study designInterventional
Study designLate phase II three-outcome non-randomised design
Secondary study designNon randomised study
Study type Participant information sheet
Scientific titlePilot 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 acronymAML Len5
Study objectivesThe 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) studiedAcute myeloid leukaemia, high-risk myelodysplastic syndrome, chromosome 5 cytogenetic abnormalities
InterventionFor 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 typeDrug
PhasePhase II
Drug / device / biological / vaccine name(s)Lenalidomide, cytosine arabinoside, daunorubicin, etoposide
Primary outcome measure(s)

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.

Key secondary outcome measure(s)

1. Time to recovery of neutrophils
2. Blood product usage
3. Length of time spent in hospital

Completion date31/12/2009

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration39
Total final enrolment14
Key inclusion criteria1. 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 criteria1. 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 enrolment01/01/2009
Date of final enrolment31/12/2009

Locations

Countries of recruitment

  • United Kingdom
  • England

Study participating centre

St James's Institute of Oncology
Leeds
LS9 7DF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summary
IPD sharing planNot 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
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
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.

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