Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma (HO95)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01208766|
Recruitment Status : Active, not recruiting
First Posted : September 24, 2010
Last Update Posted : March 24, 2021
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
Study phase: phase III
- Comparison of Bortezomib, Melphalan, Prednisone (VMP) with High Dose Melphalan followed autologous stem cell transplantation (ASCT)
- Comparison of Bortezomib, Lenalidomide, Dexamethasone(VRD) as consolidation versus no consolidation
- Comparison of single versus tandem high dose Melphalan with ASCT
Patient population: Patients with symptomatic multiple myeloma,previously untreated, ISS stages 1-3, age 18-65 years inclusive
Study design: Prospective, multicenter, intergroup, randomized
Duration of treatment: Expected duration of induction, stem cell collection and intensification is 6 - 9 months. Consolidation with VRD will last 2 months Maintenance therapy with Lenalidomide will be given until relapse. All patients will be followed until 10 years after registration.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Bortezomib, Melphalan, Prednisone (VMP) Drug: 1 or 2 cycle(s) HDM (High Dose Melphalan) Drug: 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1503 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase III Study to Compare Bortezomib, Melphalan, Prednisone (VMP) With High Dose Melphalan Followed by Bortezomib, Lenalidomide, Dexamethasone (VRD) Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma|
|Actual Study Start Date :||January 2011|
|Actual Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||April 2023|
Active Comparator: R1: 4 cycles Bortezomib, Melphalan, Prednisone (VMP)
All patients randomized to VMP treatment, will be treated with Bortezomib, Melphalan, Prednisone(VMP, 4 cycles) and will start intensification with VMP between 4 and 6 weeks after stem cell collection.
Drug: Bortezomib, Melphalan, Prednisone (VMP)
Experimental: R1: 1 (2) cycle(s) HDM
All patients randomized to intensification with High Dose Melphalan will start intensification with HDM (in hospitals with a policy of double intensification, patients will be randomized between VMP, 1 HDM and 2 HDM) between 4 and 6 weeks after stem cell collection.
Drug: 1 or 2 cycle(s) HDM (High Dose Melphalan)
- Melphalan _ 100 mg/m² _ i.v. rapid infusion _ -3, -2*
*Patients with renal insufficiency 100 mg/m2 only at day -3
If a patient is randomized to receive 2 x HDM a second course of High Dose Melphalan may be administered between 2 and 3 months after the first course when the patient achieved at least PR.
No Intervention: R2: none
No consolidation, patients will continue to Lenalidomide maintenance.
Experimental: R2: 2 cycles of VRD
In patients randomized to consolidation treatment, 2 cycles of Bortezomib, Lenalidomide,Dexamethasone (VRD) will start at 8 weeks after the end of the last course of VMP or HDM.
Drug: 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)
- For all registered patients: progression free survival (PFS) as defined by time from registration to progression or death from any cause (whichever occurs first). [ Time Frame: end of trial (last patient last visit) ]
- For all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first [ Time Frame: end of trial (last patient last visit) ]
- For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes first [ Time Frame: end of trial (last patient last visit) ]
- Overall survival measured from the time of registration /randomization R1/ randomization R2. Patients still alive or lost to follow up are censored at the date they were last known to be alive. [ Time Frame: end of trial (last patient last visit) ]
- Toxicity [ Time Frame: End of trial (last patient last visit) ]
- Response (PR, VGPR, CR and stringent CR), and improvement of response during the various stages of the treatment. [ Time Frame: end of trial (last patient last visit) ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years to 65 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Patients with a confirmed diagnosis of symptomatic multiple myeloma stage I to III according to the International Staging System ISS (see appendix A), i.e. at least one of the CRAB criteria should be present;
- Measurable disease as defined by the presence of M-protein in serum or urine (serum M-protein> 10 g/l or urine M-protein > 200 mg/24 hours), or abnormal free light chain ratio;
- Age 18-65 years inclusive;
- WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by comorbid conditions);
- Negative pregnancy test at inclusion if applicable;
- Written informed consent.
Inclusion for randomisation 1:
- WHO performance 0-2;
- Bilirubin and transaminases < 2.5 times the upper limit of normal values;
- A suitable stem cell graft containing at least 4 x 106 CD34+ cells/kg (or according to national guidelines).
Inclusion for randomisation 2:
- Bilirubin and transaminases < 2.5 times the upper limit of normal values;
- ANC >= 0.5 x 109/l and platelets > 20 x 10^9/l;
- Patient is able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan.
- Known intolerance of Boron;
- Systemic AL amyloidosis;
- Primary Plasmacell Leukemia;
- Non-secretory MM;
- Previous chemotherapy or radiotherapy except local radiotherapy in case of local myeloma progression or corticosteroids maximum 5 days for symptom control;
- Severe cardiac dysfunction (NYHA classification II-IV);
- Significant hepatic dysfunction, unless related to myeloma;
- Patients with GFR <15 ml/min,
- Patients known to be HIV-positive;
- Patients with active, uncontrolled infections;
- Patients with neuropathy, CTC grade 2 or higher;
- Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
- Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women);
- Lactating women.
Exclusion for randomisation 1:
- Severe pulmonary, neurologic, or psychiatric disease;
- CTCAE grade 3-4 polyneuropathy during Bortezomib treatment;
- Allogeneic Stem Cell Transplantation (Allo SCT) planned;
- Progressive disease.'
Exclusion for randomisation 2:
- Progressive disease;
- Neuropathy, except CTCAE grade 1;
- CTCAE grade 3-4 polyneuropathy during Bortezomib treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01208766
|Principal Investigator:||Pieter Sonneveld, Prof.||Stichting Hemato-Oncologie voor Volwassenen Nederland|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Stichting Hemato-Oncologie voor Volwassenen Nederland|
|Other Study ID Numbers:||
HOVON 95 MM
2009-017903-28 ( EudraCT Number )
EMN02 ( Other Identifier: European Myeloma Network )
|First Posted:||September 24, 2010 Key Record Dates|
|Last Update Posted:||March 24, 2021|
|Last Verified:||March 2021|
Multiple Myeloma (Kahler's disease)
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Blood Protein Disorders
Immune System Diseases
Peripheral Nervous System Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal