Additional identifiers
EudraCT number
2009-012033-30
ClinicalTrials.gov number
Protocol/serial number
7268
Study information
Scientific title
Phase II study of the adjuvant use of lenalidomide in patients undergoing reduced intensity conditioning allogenic transplantation for multiple myeloma
Acronym
LenaRIC
Study hypothesis
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
First MREC approval date 12/11/2010, ref 10/H1208/49
Study design
Non-randomised interventional trial
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
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
Phase
Phase II
Drug names
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 trial start date
01/05/2011
Overall trial end date
19/12/2017
Reason abandoned (if study stopped)
Eligibility
Participant 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.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
40 patients
Participant 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
Recruitment start date
31/05/2011
Recruitment end date
12/06/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
Sponsor information
Organisation
University Hospitals Birmingham NHS Foundation Trust (UK)
Sponsor details
c/o Miss Shamyla Siddique
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK Feasibility Study Committee
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
Celgene Ltd (unrestricted educational grant)
Alternative name(s)
Celgene Corporation
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal late 2017 – early 2018.
IPD sharing statement
The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
19/03/2018
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list