The MM5 trial: evaluation of two regimens of bortezomib-based induction therapy and of lenalidomide consolidation followed by lenalidomide maintenance treatment in patients with multiple myeloma

ISRCTN	ISRCTN05622749
DOI	https://doi.org/10.1186/ISRCTN05622749
Protocol serial number	MM5
Sponsor	University Hospital Heidelberg (Universitätsklinikum Heidelberg) (Germany)
Funders	Celgene (Europe), Janssen Cilag (Europe), Chugai (Germany), The Binding Site (Germany), University Hospital Heidelberg (Universitätsklinikum Heidelberg) (Germany)

Submission date: 16/04/2010
Registration date: 27/04/2010
Last edited: 18/11/2025

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

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

Primary study design	Interventional
Study design	Prospective multicentre multinational randomised parallel group open phase III clinical trial
Secondary study design	Randomised controlled trial
Scientific title	Randomised phase III trial for previously untreated multiple myeloma to evaluate two regimens of bortezomib based induction therapy and lenalidomide consolidation followed by lenalidomide maintenance treatment
Study acronym	MM5
Study objectives	The MM5 trial is designed to address two independent primary objectives. The primary objectives of the study are: 1. Demonstration of non-inferiority of VCD (bortezomib, cyclophosphamide, dexamethasone) induction therapy compared to PAd (bortezomib, adriamycin, dexamethasone) induction therapy with respect to response rate (very good partial remission or better; response criteria of the International Myeloma Working Group [IMWG]) 2. Determination of the best of four treatment strategies with respect to progression-free survival (PFS). The four treatment strategies are defined by PAd versus VCD induction treatment, standard intensification therapy, lenalidomide consolidation and maintenance treatment with lenalidomide for 2 years versus lenalidomide until complete response (CR).
Ethics approval(s)	Ethikkommission der Medizinischen Fakultaet Heidelberg, University of Heidelberg, pending as of 16/04/2010
Health condition(s) or problem(s) studied	Multiple myeloma
Intervention	Patients are randomised into four treatment arms (A1, A2, B1, B2). Patients included in arms A1/B1 are treated with 3 cycles PAd (bortezomib 1.3 mg/m^2 intravenous [iv] on days 1, 4, 8 and 11, doxorubicin 9 mg/m^2 iv on days 1 - 4, dexamethasone [Dex] orally [po] 20 mg/d on days 1 - 4, 9 - 12 and 17 - 20). Patients in arm A2/B2 are treated with 3 cycles VCD (bortezomib 1.3 mg/m^2 iv on days 1, 4, 8 and 11, cyclophosphamide 900 mg/m^2 iv on day 1, dexamethasone po 40 mg/d on days 1 - 2, 4 - 5, 8 - 9, 11 - 12). Standard intensification treatment will be done according to local protocols. Thereafter, two cycles of lenalidomide 25 mg/d on days 1 - 21 are given, followed by a lenalidomide maintenance treatment (lenalidomide orally [po] 10 mg/d in the first three months, thereafter 15 mg/d). In arms A1 and A2 lenalidomide maintenance will be given for a period of 2 years, in arms B1 and B2 until a CR is reached.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	VCD (bortezomib, cyclophosphamide, dexamethasone), PAd (bortezomib, adriamycin, dexamethasone)
Primary outcome measure(s)	1. Response to treatment (very good partial remission or better) after induction therapy, measured after induction therapy 2. Progression-free survival (i.e., time from randomisation to progression or death from any cause whichever occurs first), measured at several timepoints during study and follow up if there is a progression of the disease
Key secondary outcome measure(s)	1. Overall survival defined as time from randomisation to death from any cause. Patients still alive or lost to follow up are censored at the date they were last known to be alive. 2. Response rates (response rates will be assessed using the following subcategories: SD, MR, PR, VGPR [with subgroup nCR], CR, sCR, mCR). Response measured after induction, after intensification, after consolidation and during maintenance. 3. Toxicity ([serious] adverse events CTC grade 3 and grade 4, CTC-AE v4.0), measured at induction, consolidation and maintenance treatment
Completion date	11/03/2017

Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	18 Years
Upper age limit	100 Years
Sex	All
Target sample size at registration	504
Key inclusion criteria	1. Confirmed diagnosis of multiple myeloma requiring systemic therapy 2. Measurable disease 3. Aged 18 - 70 years inclusive, either sex
Key exclusion criteria	1. Previous chemotherapy or radiotherapy during the past 5 years except local radiotherapy in case of local myeloma progression 2. Severe cardiac dysfunction 3. Significant hepatic dysfunction 4. Patients known to be human immunodeficiency virus (HIV)-positive 5. Patients with active, uncontrolled infections 6. Patients with peripheral neuropathy or neuropathic pain, Common Toxicity Criteria (CTC) grade 2 or higher 7. Patients with a history of active malignancy during the past 5 years 8. Systemic amyloid light chain (AL) amyloidosis 9. Pregnancy and lactation
Date of first enrolment	26/07/2010
Date of final enrolment	14/11/2013

Locations

Countries of recruitment

France
Germany

Study participating centre

Universitätsklinikum Heidelberg

Heidelberg
69120
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	01/08/2015	29/01/2019	Yes	No
Results article	01/07/2020	10/02/2020	Yes	No
Other publications	11/11/2025	18/11/2025	Yes	No

Editorial Notes

18/11/2025: Publication reference added.
10/02/2020: Publication reference added.
30/01/2019: The following changes have been made to the trial record:
1. Publication reference added
2. The overall trial start date has been changed from 15/05/2010 to 01/10/2008
3. The recruitment start date has been changed from 15/05/2010 to 26/07/2010
4. The recruitment end date has been changed from 15/05/2016 to 14/11/2013
5. The overall trial end date has been changed from 15/05/2016 to 11/03/2017