Patients, 18-65 years, inclusive, multiple myeloma with a first relapse or progression after first line therapy (with a HLA- identical sibling or unrelated donor completely matched (10/10)) MedDRA version: 14.1 Level: PT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: bortezomib
Pharmaceutical Form: Powder for injection
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
C
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with multiple myeloma with a first relapse or with progression after first line therapy; • Relapsed or progressive patients have received reinduction therapy before entering this trial; • At least PR after reinduction treatment; • 18-65 years,inclusive; • HLA-identical sibling or unrelated donor completely matched (10/10) (excluding identical twins); • WHO-performance status 0-2; • Written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: • No previous Allo-SCT; • Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D); • Severe neurological or psychiatric disease; • Patients with neuropathy, CTC grade 3 or higher; • Significant hepatic dysfunction (serum bilirubin or transaminases = 3 times upper limit of normal); • Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration); • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.); • History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or or carcinoma “in situ” of the cervix or breast; • Patient known to be HIV-positive; • Patients with brain disease with the exception of those patients whose brain disease has been treated with either radiotherapy or surgery and remains asymptomatic, with no active brain disease, as shown by CT scan or MRI, for at least 6 months; • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide or borium; • Pregnant or breast-feeding female patients. Negative pregnancy test at study is mandatory for female patients of childbearing potential; • Not able and not willing to use adequate contraception during therapy; • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule; • Severe cardiac dysfunction (NYHA classification II-IV, see appendix E).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assessment of feasibility and toxicity of T cell depleted NMA Allo-SCT followed by lenalidomide or lenalidomide combined with bortezomib,and subsequent DLI; as treatment of relapsed multiple myeloma after first line therapy who are at least in PR after reinduction therapy;Secondary Objective: • To assess the efficacy of early consolidation as determined by response and number of patients that receive subsequent DLI. • To assess the overall efficacy of the regimen as determined by response rate (especially CR), progression free survival and overall survival. • To evaluate quality of life with these regimens.;Primary end point(s): Failure free duration (FFD) at 9 months post-transplant. Patients count as a failure (= event) at the earliest time point at which any of the following events occurs within 9 months after Allo-SCT : - Onset of acute GvHD grade 3-4 without prior DLI; - Onset of extensive chronic GvHD without prior DLI; - Non-hematological toxicity CTCAE grade 4; - Systemic therapy for uncontrolled myeloma other than the assigned study treatment of lenalidomide or lenalidomide/bortezomib and DLI; - Death not due to (progression of) MM, which is in fact TRM. Patients without a failure within 9 months post Allo-SCT will be censored at 9 months, at the date of progression, or when they go off protocol treatment, whichever comes first. ;Timepoint(s) of evaluation of this end point: If the trial was not discontinued early, the final analysis will be performed when complete information is available for all eligible patients in a treatment arm. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Toxicity profile and compliance related to each treatment step and intervals between treatment steps (Allo-SCT, consolidation chemotherapy as well as pre-emptive DLI); • Percentage of patients with a pre-emptive DLI within 6-9 months from the date of Allo-SCT; • Response, improvement of response and conversion to full donor chimerism during the separate treatment phases (i.e. from Allo-SCT until consolidation; from consolidation to DLI; and after DLI); • CR rate; • Progression-free survival (PFS; i.e. time from registration until progression, relapse or death, whichever comes first); • PFS from Allo-SCT; • Overall survival (OS) measured from time of registration; • OS from Allo-SCT; • The poportion of patients that complete 1, 2 resp. 3 induction cycles; • Quality of life as defined by the EORTC QLQ-C30 and QLQ-MY20 ;Timepoint(s) of evaluation of this end point: If the trial was not discontinued early, the final analysis will be performed when complete information is available for all eligible patients in a treatment arm. | — |
Countries
Netherlands
Contacts
Public ContactHOVON Data Center
HOVON
Outcome results
None listed