HOVON HO95 MM
- HOVON 95 MM / EMN02
- Working group party:
- 1st lijn
- Level D
- Included patients:
- Active sites:
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.
- For data management go to the EMN website: (http://www.mm-sen.net/)
- Sampling (at relapse/progression to central lab) IMPORTANT: it is not possible to ship material on a Friday, Saturday or Sunday. If your hospital routinely has multiple myeloma patient appointments for obtaining clinical samples on these days, please inform the PI and please change the planning. Seeing patients for MM biomaterial sampling on a Friday or on the weekend is in direct conflict with participating in a clinical trial such as this one.
- The study has been closed for inclusion on 15APR14, many thanks for your precious collaboration to make this into a highly successfull study! Of course patients included can still receive maintenance treatment.
- AM8 (protocol version 7 dd 04DEC2019) has been approved in the Netherlands. Maintenance therapy until progression; data collection during 10 years instead of 7 years.
- AM5 (protocol version 6 dd 06MAY14) has been approved. Change in treatment schedule Lenalidomide during maintenance from 28 days to 21 days followed by 7 days rest. Further information can be found in the summery of changes form.
- AM4 (protocol version 5 dd 15JAN13) has been approved. The Lenalidomide doses 2.5mg and 7.5mg has been deleted from the protocol.
- AM3 has been approved, the main changes were 4VCD cycles and Velcade s.c. Please find more information in the summary of changes documents.
- AM2 has been approved, this concerns the new packaging of Lenalidomide. The new batch will not have vials with capsules, but has blisters with separately packed capsules in a press-through sheet.
- AM1 concerned the addition of the Belgium site ZNA Stuivenberg and the integrations of adverse events of lenalidomide including the risk of 2nd cancer
- Updated documents:
28MAY2020: Updated CRF instructions
14JAN2020: Updated SAE form with new fax number
27MAR2017: Updated Lenalidomide accountability form, to add 'Returned by patient' as option, so that this part of the accountability is not forgotten.
14DEC15: Updated Pharmacy information letter to reflect usage of IDOS + uploade IDOS instructions below other documents
18NOV15: Renewed drug order form for Lenalidomide
29SEP14: Deletion of subject enrollement list to make room for QoL declaration form (please note, this can only be used by Dutch sites.
30JUL14: Deletion of Registrate Enroll and Randomization CRF's_26NOV12, replacement by separate Randomization 1 and Randomization 2 CRF
16JUL14: New protocol (version 6) + summery of changes, updated portfolio regarding EC and CA approval for the Netherlands
15MAY14: New Statement of expenses form for Dutch sites for QoL
14MAY14: New Dutch WMO insurance (enddate of insurance changed to 2018)
08APR14: New FAQ sheet, correctie versie 20MAR14
11NOV13: New Pharmacy information letter dated 11NOV13
21OCT13: New FAQ sheet
19JUN13: New Pharmacy information letter dated 19JUN13
03SEP13: New portfolios created for BE (site documents, EC and CA portfolio)
11JUN13: New Insurance policy BE (valid util 31DEC13)
05FEB13: New Pharmacy information letter dated 05FEB13
22JAN13: New Registrate Enroll and Randomization CRFs_26NOV12.pdf
07DEC12: New documents regarding AM3
- Protocol amendment(s)
- Patient Information & IC form (NL)
- Patient Information & IC form (EN)
- PI & ICF amendment(s)
- CCMO response
- MEC approval
- Signature page of protocol
- HO95 ICF template asymptomatic patients nl v2 13jun12 cc
- HO95 ICF asymptomatic patients summary of changes am3 dd 20jun12
- HO95 ICF template extra sampling nl v1 13jun12
- EMN02 HO95 ICF alloSCT substudy v2 dd 25jun12 cc
- HO95 ICF template pet scan substudy nl v1 13jun12
- HO95 Flowchart_12DEC12
28OCT12: SAE form
16OCT12: New FAQ sheet
16JUL12: CRF instructions
19JUN12: SAE instuctions
29MAY12: New pharmacy information letter (includes also the option to order Lenalidomide per quarter of the year - was previously only accepted for Bortezomib)
29MAR12: 'onderzoeksverklaring' to be used for Dutch sites that did not perform their local submission yet
16MAR12: New declaration form of expenses (previous version was lacking contact information)
01MAR12: New pharmacy information letter (reflects the adjusted Lenalidomide study medication procedure)
16FEB12: EC Approval (portfolio) with AM2 approval
25NOV11: EMN02 HO95 eCRF printscreen versions_19AUG11.pdf
25NOV11: New version of EMN02 HO95_Registrate, Enroll and Randomization CRFs_25OCT11.pdf
27JUL11: HO95_creation of subaccounts_07JUL11.pdf (new)
27JUL11: EMN02 HO95 eCRF printscreen versions_13JUL11.pdf (new)
27JUL11: New version of EMN02 HO95_Registrate, Enroll and Randomization CRFs_07JUL11_clean version.pdf (replaces the one dated 28APR11)
16JUN11: New Verpleegkundig protocol dated 16JUN11 (replaces the one dated 28APR11)
15JUN11: New Pharmacy information letter dated 07JUN11 (replaces the one dated 19APR11)
- Prospective randomized Phase III study
- Monitoring Type:
- Not any more
- Efficacy of FCM in correction of ID (TSAT >=20%)
- Impact of FCM on quality of life (EORTC QLQ-C30)
Impact of FCM on:
- Haemoglobin levels during induction therapy
- Number of stem cells collected
- Transfusion rate during induction
- Transfusion rate after stem cell transplantation (<21 days)
- Response to VCD induction chemotherapy
- Inclusion Criteria:
- 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 Mproteïn > 10 g/l or urine M-proteïn > 200 mg/24 hours or abnormal FLC ratio with involved free light chain (FLC) > 100 mg/l) or proven plasmacytoma by biopsy;
- Age 18-65 years inclusive;
- WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by comorbid conditions) (see appendix D);
- Negative pregnancy test at inclusion if applicable;
- Written informed consent.
Inclusion criteria for randomization 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 10^6 CD34+ cells/kg (or according to national guidelines).
Inclusion criteria for randomization 2:
- Bilirubin and transaminases < 2.5 times the upper limit of normal values;
- ANC ≥ 0.5 x 10^9/l and platelets > 20 x 10^9/l;
- Patient is able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan.
- Exclusion Criteria:
- 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, see appendix E);
- Significant hepatic dysfunction (serum bilirubin ≥ 30 μmol/l or transaminases ≥ 2.5 times normal level), 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 criteria for randomization 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 criteria for randomization 2:
- Progressive disease;
- Neuropathy, except CTCAE grade 1;
- CTCAE grade 3-4 polyneuropathy during Bortezomib treatment.
The patient should be registered immediately after diagnosis and before the start of chemotherapy.
Patients will be registered at the EMN Data Center by web http://www.mm-sen.net. Investigators who do not have an account yet should register at this website to obtain an account.
The following information will be requested at registration:
- Institution name
- Name of responsible investigator
- Date of birth
- Date of informed consent
- Date of sample shipment (optional)
- Date of diagnosis of multiple myeloma
- Criteria for measurable disease
- Serum β2-microglobulin
- Serum albumin
- Eligibility criteria
Final analysis VRD randomization (Q2/Q3-2020)
Ziekenhuizen die deelnemen aan het onderzoek staan benoemd op de HOVON website bij het onderzoek. Het kan zijn dat uw ziekenhuis niet genoemd wordt, maar wel aan het onderzoek deelneemt. Informeer hiernaar bij uw arts.