Lenalidomide and dexamethasone with or without high-dose melphalan and autologous blood stem cell transplantation followed by lenalidomide maintenance in the treatment of relapsed multiple myeloma

ISRCTN	ISRCTN16345835
DOI	https://doi.org/10.1186/ISRCTN16345835
Secondary identifying numbers	ReLApsE_RV-MM-GMMG-340

Submission date: 24/08/2010
Registration date: 06/09/2010
Last edited: 06/10/2016

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Hartmut Goldschmidt
Scientific

Universitätsklinikum Heidelberg
Medizinische Klinik V und Nationales Centrum für Tumorerkrankungen (NCT)
Im Neuenheimer Feld 410
Heidelberg
69120
Germany

Study information

Study design	Randomised open-label multicentre phase III trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
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	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
Study acronym	ReLApsE
Study objectives	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(s)	Ethikkommission der Medizinischen Fakultaet Heidelberg, University of Heidelberg, 12/03/2010
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	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 study start date	27/09/2010
Completion date	30/06/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	282
Key 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
Key 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
Date of first enrolment	27/09/2010
Date of final enrolment	30/06/2017

Locations

Countries of recruitment

Germany

Study participating centre

Universitätsklinikum Heidelberg

Heidelberg
69120
Germany

Sponsor information

University Hospital Heidelberg (Universitätsklinikum Heidelberg) (Germany)
Not defined

Im Neuenheimer Feld 672
Heidelberg
69120
Germany

Website	http://www.klinikum.uni-heidelberg.de/
"ROR"	https://ror.org/013czdx64

Funders

Funder type

Industry

Celgene (Europe)
Private sector organisation / For-profit companies (industry)

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

Dietmar-Hopp-Foundation (Germany)

No information available

Chugai (Germany)

No information available

Amgen (Germany)
Government organisation / For-profit companies (industry)

Alternative name(s): Amgen Inc., Applied Molecular Genetics Inc.
Location: United States of America

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

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	25/04/2016		Yes	No

Editorial Notes

06/10/2016: The overall trial end date was changed from 26/09/2015 to 30/06/2017.
27/04/2016: Publication reference added.