Phase II study of the adjuvant use of lenalidomide in patients undergoing reduced intensity conditioning allogenic transplantation for multiple myeloma

ISRCTN	ISRCTN16228367
DOI	https://doi.org/10.1186/ISRCTN16228367
EudraCT/CTIS number	2009-012033-30
Secondary identifying numbers	7268

Submission date: 24/05/2011
Registration date: 24/05/2011
Last edited: 28/05/2020

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

http://cancerhelp.cancerresearchuk.org/trials/trials-search/a-trial-looking-lenalidomide-after-stem-cell-transplant-for-people-with-myeloma-lenaric

Study website

Contact information

Miss Shamyla Siddique
Scientific

Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom

Study information

Study design	Non-randomised interventional trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	http://www.birmingham.ac.uk/research/activity/mds/trials/crctu/trials/haematology/lenaric/investigators.aspx
Scientific title	Phase II study of the adjuvant use of lenalidomide in patients undergoing reduced intensity conditioning allogenic transplantation for multiple myeloma
Study acronym	LenaRIC
Study objectives	Allogeneic stem cell transplant (SCT) remains the only curative option for multiple myeloma (MM). However, conventional (myeloablative) transplants remain associated with a substantial transplant related mortality which compromises effectiveness in younger patients and precludes their use entirely in patients over the age of 55 years. The recent demonstration that the use of reduced intensity conditioning (RIC) regimens substantially reduces the toxicity of allografting, whilst permitting durable donor stem cell engraftment, has raised the hope of extending this procedure to many patients who would currently not be considered for transplantation. Donor lymphocytes can be safely administered in patients who relapse late after transplantation. Routine use of donor lymphocyte infusion (DLI) early after transplant is generally avoided, as the risk of GVHD increases the sooner DLI is administered after transplant. In the context of myeloma, the strategy of delayed DLI (at one year) reduces the risk of GVHD. Consequently, an independent anti-myeloma strategy early after transplantation is required to allow sufficient delay before DLI can be safely administered. The tolerability and remarkable activity of lenalidomide against myeloma makes it an excellent candidate to be used in an adjunctive role early after a reduced intensity regimen transplant prior to later institution of DLI, to suppress the growth and rapid recovery of a residual myeloma cell population
Ethics approval(s)	First MREC approval date 12/11/2010, ref 10/H1208/49
Health condition(s) or problem(s) studied	Haematological Oncology, Myeloma
Intervention	Patients will receive up to 12 cycles of Lenalidomide (or until 12 months post-transplant). Each cycle will last 28 days and patients will receive Lenalidomide on days 1 - 21 of each 28 day cycle. Dose reductions are in place. Follow up length: 24 month(s). Study entry : registration only.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Fludarabine, lenalidomide, ciclosporin, ATG
Primary outcome measure	1. Progression free survival at 2 years post transplant 2. Timepoint(s): 2 years post transplant
Secondary outcome measures	1. Day +100 and 1 year non-relapse mortality, timepoint(s): day 100 and year 1 2. Disease free survival at 1 and 2 years post transplant, timepoint(s): Markers of disease assessed at months 1, 3, 6, 9, 12, 15, 18, 21 and 24 post transplant 3. Donor engraftment, timepoint(s): lineage-specific chimerism assessed at months 1, 3, 6, 9, 12, 15, 18, 21 and 24 post-transplant 4. GVHD, timepoint(s): GVHD will be monitored continuously until 2 years post transplant 5. Overall survival at years 1 and 2 post transplant, timepoint(s): will be monitored continuously until 24 months post-transplant
Overall study start date	01/05/2011
Completion date	19/12/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	40 patients
Total final enrolment	40
Key inclusion criteria	1. Multiple myeloma subjects who have received a high dose melphalan conditioned autologous transplant in the preceding 120 days and who are in CR1/2 or VGPR1/2 as defined by International uniform response criteria for Myeloma, 2006 (Appendix 1) 2. Patients 18 to 70 years in whom allogeneic transplantation using a reduced intensity conditioning regimen is not contra-indicated but who are not suitable for conventional allograft 3. Eastern Cooperative Oncology Group (ECOG) status <2 or an ECOG status of 3 if the reason for a status of 3 is due exclusively to multiple myeloma (e.g. pathological fracture) (Appendix 2) 4. Patients with a HLA identical sibling or ten/ten antigen (A,B,C,DR,DQ) matched unrelated donor 5. Cardiac ejection fraction > 40% 6. Measured EDTA Creatinine clearance >50 ml/min 7. Carbon Monoxide Diffusing Capacity (DLCO) >50% 8. Liver function (AST or ALT) < 2.5 x upper limit of normal 9. Patients able to give written informed consent prior to allogeneic transplant, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice 10. Patients willing and able to comply with the protocol for the duration of the study 11. Agree to abstain from donating blood (and semen in male subjects) while taking study drug therapy and for 28 days following discontinuation of study drug therapy 12. Agree not to share study drug with another person and to return all unused study drug to the investigator or pharmacist 13. Male or female 14. Upper age limit 70 years 15. Lower age limit 18 years Updated 10/07/2017: upper age limit changed from 65 to 70 years.
Key exclusion criteria	1. Patients with allergies or contraindications to receiving Fludarabine, Lenalidomide, ciclosporin or ATG 2. Pregnant or lactating women 3. Adults of reproductive potential not willing to comply with the Lenalidomide Risk Minimisation Plan 4. Patients with organ allografts 5. Any co-morbidity that, in the investigators opinion, would affect the patients participation in this study 6. Patient who have taken any other investigational medical product within 4 weeks of starting conditioning therapy Added 10/07/2017: 7. Patients with known positive serology for HIV/Hepatitis B/Hepatitis C 8. Patients who have undergone a previous allogeneic stem cell transplant 9. Patients who have previously progressed on Lenalidomide
Date of first enrolment	31/05/2011
Date of final enrolment	12/06/2015

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Queen Elizabeth Hospital

Birmingham
B15 2TH
United Kingdom

Sponsor information

University Hospitals Birmingham NHS Foundation Trust (UK)
University/education

c/o Miss Shamyla Siddique
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
England
United Kingdom

Website	http://www.uhb.nhs.uk/
"ROR"	https://ror.org/014ja3n03

Funders

Funder type

Charity

Cancer Research UK Feasibility Study Committee
Private sector organisation / Other non-profit organizations

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

Celgene Ltd (unrestricted educational grant)
Private sector organisation / For-profit companies (industry)

Alternative name(s): Celgene Corporation
Location: United States of America

Results and Publications

Intention to publish date	19/03/2018
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Planned publication in a high-impact peer reviewed journal late 2017 – early 2018.
IPD sharing plan	The current data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results			28/05/2020	No	No
HRA research summary			28/06/2023	No	No

Editorial Notes

28/05/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
11/07/2017: The overall trial end date was changed from 30/04/2015 to 19/12/2017.
10/07/2017: Funder changed from 'Clinical Trials Awards and Advisory Committee (CTAAC)' to 'Cancer Research UK Feasibility Study Committee and an unrestricted educational grant from Celgene Ltd'.