Condition category
Cancer
Date applied
28/10/2009
Date assigned
11/11/2009
Last edited
11/11/2009
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Hartmut Goldschmidt

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

GMMG-HD5

Study information

Scientific title

Phase III trial in patients with multiple myeloma to optimize bortezomib based induction (bortezomib, Adriamycin®, dexamethasone [PAd] vs. bortezomib, cyclophosphamide, dexamethasone [VCD]) prior to high dose therapy and autologous stem cell transplantation followed by lenalidomide based consolidation and maintenance therapy

Acronym

GMMG-HD5

Study hypothesis

The GMMG-HD5 trial is designed to address two independent primary objectives:
1. Demonstration of non-inferiority of VCD induction therapy compared to PAd 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, High Dose melphalan Therapy (HDT) followed by autologous stem cell transplantation and maintenance treatment with lenalidomide for 2 years versus lenalidomide until complete remission (CR).

Ethics approval

Ethikkommission der Medizinischen Fakultaet Heidelberg, University of Heidelberg, submission planned for November 2009

Study design

Prospective multicentre multinational randomised parallel group open phase III clinical 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

Multiple myeloma

Intervention

1. Patients are randomised into four treatment arms (A1, A2, B1, B2)
2. 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)
3. 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)
4. Stem cells are mobilised by CAD (cyclophosphamide iv 1 g/m^2 on day 1, doxorubicin 15 mg/m^2 iv on days 1 – 4, Dex po 40 mg/d on days 1 - 4) and G-CSF. At least 5 x 10^6 CD34+ cells/kg body weight have to be harvested.
5. High dose therapy (HDT, melphalan 200 mg/m^2) is started 4 - 6 weeks after CAD
6. For patients not reaching a CR after HDT1, a second HDT is performed within 2 – 3 months after HDT1. Thereafter, two cycles of lenalidomide 25 mg/d on days 1 - 21 are given, followed by a lenalidomide maintenance treatment (lenalidomide po 10 mg/d in the first three months, thereafter 15 mg/d).
7. 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 names

PAd (bortezomib/PS341 [Velcade®], doxorubicin [Adriamycin®], dexamethasone), VCD (bortezomib, cyclophosphamide, dexamethasone), melphalan, lenalidomide

Primary outcome measures

1. Response to treatment (very good partial remission or better) after induction therapy
2. Progression free survival (i.e., time from randomisation to progression or death from any cause, whichever occurs first)
Patients will be investigated for progression after every treatment phase (induction, HDT, consolidation) and then every 3 months in maintenance treatment and follow up

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 to be measured after induction, after transplantation, after consolidation and during maintenance
2.1. Partial remission (PR)
2.2. Very good partial remission (VGPR)
2.3. Complete remission (CR)
2.4. Molecular complete remission (mCR)
3. Toxicity ([serious] adverse events CTC grade 3 and grade 4, CTC-AE v4.0) related to induction, consolidation and maintenance treatment
4. Progression free survival from HDT (i.e., time from last HDT treatment to progression or death from any cause whichever occurs first)

Overall trial start date

01/01/2010

Overall trial end date

01/01/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Confirmed diagnosis of multiple myeloma requiring systemic therapy
2. Measurable disease
3. Age 18 - 70 years inclusive, either sex

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

504

Participant 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 AL amyloidosis

Recruitment start date

01/01/2010

Recruitment end date

01/01/2016

Locations

Countries of recruitment

France, Germany

Trial participating centre

Universitätsklinikum Heidelberg
Heidelberg
69120
Germany

Sponsor information

Organisation

Heidelberg University (Germany)

Sponsor details

Im Neuenheimer Feld 672
Heidelberg
69120
Germany

Sponsor type

University/education

Website

http://www.uni-heidelberg.de/index_e.html

Funders

Funder type

Industry

Funder name

Celgene (Eurpope) (ref: RV-MM-GMMG-0423)

Alternative name(s)

Celgene Corporation

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Funder name

Janssen Cilag (Europe) (ref: 26866138MMY3026)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Chugai (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Binding Site (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

University Hospital Heidelberg (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes