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 |
| Secondary identifying numbers | MM5 |
- Submission date
- 16/04/2010
- Registration date
- 27/04/2010
- Last edited
- 10/02/2020
- 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
Not provided at time of registration
Contact information
Prof Hartmut Goldschmidt
Scientific
Scientific
Universitätsklinikum Heidelberg
Medizinische Klinik V und Nationales Centrum für Tumorerkrankungen (NCT)
Im Neuenheimer Feld 410
Heidelberg
69120
Germany
Study information
| Study design | Prospective multicentre multinational randomised parallel group open phase III clinical 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 | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | VCD (bortezomib, cyclophosphamide, dexamethasone), PAd (bortezomib, adriamycin, dexamethasone) |
| Primary outcome measure | 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 |
| Secondary outcome measures | 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 |
| Overall study start date | 01/10/2008 |
| Completion date | 11/03/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 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
69120
Germany
Sponsor information
University Hospital Heidelberg (Universitätsklinikum Heidelberg) (Germany)
Hospital/treatment centre
Hospital/treatment centre
Im Neuenheimer Feld 672
Heidelberg
69120
Germany
| Website | http://www.med.uni-heidelberg.de/ |
|---|---|
"ROR" |
https://ror.org/013czdx64 |
Funders
Funder type
Industry
Celgene (Europe)
Private sector organisation / For-profit companies (industry)
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Celgene Corporation
- Location
- United States of America
Janssen Cilag (Europe)
No information available
Chugai (Germany)
No information available
The Binding Site (Germany)
No information available
University Hospital Heidelberg (Universitätsklinikum Heidelberg) (Germany)
No information available
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? |
|---|---|---|---|---|---|
| Results article | results | 01/08/2015 | 29/01/2019 | Yes | No |
| Results article | results | 01/07/2020 | 10/02/2020 | Yes | No |
Editorial Notes
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
