Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
ReLApsE_RV-MM-GMMG-340
Study information
Scientific title
A phase III national, multicentre, randomised open-label study with lenalidomide/dexamethasone versus lenalidomide/dexamethasone followed by high-dose chemotherapy melphalan with autologous blood stem cell transplantation and lenalidomide maintenance therapy for patients with relapsed multiple myeloma
Acronym
ReLApsE
Study hypothesis
The aim of this trial is to demonstrate a significant improvement of progression-free survival in patients treated with lenalidomide/dexamethasone induction therapy followed by high-dose chemotherapy melphalan and lenalidomide maintenance compared to conventional therapy with lenalidomide/dexamethasone.
Ethics approval
Ethikkommission der Medizinischen Fakultaet Heidelberg, University of Heidelberg, 12/03/2010
Study design
Randomised open-label multicentre phase III trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Relapsed multiple myeloma
Intervention
Patients are randomised into two treatment arms (A and B).
Standard arm A:
Rd until disease progression. Rd = lenalidomide 25 mg orally (po) days 1 - 21 and day 28 + dexamethasone 40 mg po day 1, 8, 15, 22 and 28.
Experimental arm B:
Induction therapy with 3 cycles Rd. Rd = lenalidomide 25 mg orally (po) days 1 - 21 and day 28 + dexamethasone 40 mg po day 1, 8, 15, 22 and 28. Then high dose melphalan (200 mg/m^2) with autologous peripheral blood stem cell transplantation (PBSCT) followed by lenalidomide maintenance (10 mg/day) until disease progression.
The total duration of treatment is a maximum of 5 years, the end of trial is defined 2 years after inclusion of last patient in the trial.
Intervention type
Drug
Phase
Phase III
Drug names
Lenalidomide, dexamethasone, melphalan
Primary outcome measure
Progression-free survival: time from randomisation until disease progression or death from any cause whichever occurs first. This is measured at several timepoints during study and follow up if there is a progression of the disease.
Secondary outcome measures
1. Overall survival (time from randomisation until death from any cause or date last contact)
2. Response rate (subcategories: minimal response [MR], partial response [PR], very good partial response [VGPR], complete response [CR]), measured after third and fifth cycle Rd and every three months during maintenance (Arm A) and measured after third cycle Rd, after high dose melphalan and every three months during maintenance (Arm B)
3. Feasibility of stem cell collection
4. Assessment of safety and toxicity. measured from inclusion until 30 days after last dose
5. Time to initiation of new myeloma treatment
Overall trial start date
27/09/2010
Overall trial end date
30/06/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Understand and voluntarily sign an informed consent form (aged greater than or equal to 18 years at time of signature)
2. Aged greater than or equal to 18 years and less than or equal to 70 years at time of randomisation, either sex
3. Able to adhere to the study visit schedule and other protocol requirements
4. Patients with relapsed multiple myeloma (1.-3. relapse) Salmon-Durie-Stage II or III requiring systemic therapy
5. World Health Organization (WHO) performance status less than or equal to 2 at study entry
6. Results of laboratory assessments at time of inclusion within these ranges
6.1. Absolute neutrophil count greater than or equal to 1.0 x 10^9/L
6.2. Platelet count greater than or equal to 75 x 10^9/L (if plasma cell infiltration of bone marrow less than 50%; platelets greater than or equal to 30 x 10^9/L if plasma cell infiltration of bone marrow greater than or equal to 50%)
6.3. Creatinine-Clearance greater than or equal to 30 mL/min
6.4. Total bilirubin less than or equal to 2 x upper limit of normal (ULN) (unless myeloma related)
6.5. Alanine aminotransferase (ALT) less than or equal to 3 x ULN (unless myeloma related)
7. Willing to adhere to requirements of Pregnancy Prevention Program
8. Disease free of other malignancies for greater than or equal to 5 years (exceptions include: basal cell carcinoma, carcinoma in situ of skin, cervix or breast)
9. Able to perform thromboprophylaxis with low molecular weight heparin
10. Patients who received high-dose chemotherapy and autologous stem cell transplantation in first-line therapy are eligible if they had no disease progression/relapse less than 12 months after transplantation
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
282
Participant exclusion criteria
1. Pregnant or breast feeding female
2. Non-secretory myeloma (with normal FLC-ratio)
3. Systemic AL-amyloidosis with organ involvement (except for AL-amyloidosis of skin and/or bone marrow)
4. Received treatment with any non-market drug substance within 28 days prior to start of study treatment
5. Known hypersensitivity to thalidomide or to any constituent compounds of Lenalidomide (Revlimid, e.g. lactose)
6. Development of erythema nodosum, if characterised by a desquamating rash while taking thalidomide or similar drugs
7. Active uncontrolled infection
8. Known positivity for human immunodeficiency virus (HIV) or clinically active hepatitis B or C
9. Heart insufficiency New York Heart Association (NYHA) greater than or equal to 3
10. Any serious pulmonary, neurological or psychiatric disease
11. Patient with plasma cell leukaemia
12. Previous allogeneic transplantation
13. Previous therapy with lenalidomide
14. Previous salvage autologous transplantation
Recruitment start date
27/09/2010
Recruitment end date
30/06/2017
Locations
Countries of recruitment
Germany
Trial participating centre
Universitätsklinikum Heidelberg
Heidelberg
69120
Germany
Sponsor information
Organisation
University Hospital Heidelberg (Universitätsklinikum Heidelberg) (Germany)
Sponsor details
Im Neuenheimer Feld 672
Heidelberg
69120
Germany
Sponsor type
Not defined
Website
Funders
Funder type
Industry
Funder name
Celgene (Europe)
Alternative name(s)
Celgene Corporation
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
Funder name
Dietmar-Hopp-Foundation (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Chugai (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Amgen (Germany)
Alternative name(s)
Amgen Inc., Applied Molecular Genetics Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
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
Basic results (scientific)
Publication list
2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/27114074