Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma

• Status: Active, not recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Study phase: phase III

Study objective:

• 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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stichting Hemato-Oncologie voor Volwassenen Nederland
• Collaborators: Central European Myeloma Study Group; DSMM (Deutsche Studiengruppe Multiples Myelom); European Myeloma Network; GIMEMA (Italian Group for Adult Hematologic Diseases); Gruppo Italiano Malattie EMatologiche dell'Adulto; NMSG (Nordic Myeloma Study Group)
• Treatments: BB 1101; Bortezomib; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Lenalidomide; Melphalan; Prednisone; Thalidomide

Criteria

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 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.

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);

• 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.