Multiple Myeloma
Conditions
Interventions
Induction therapy with 9 cycles of ixazomib, daratumumab and dexamethasone,
followed by maintenance therapy with ixazomib and daratumumab until progression
for a maximum period of two years
Sponsors
HOVON
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Previously untreated patients with a confirmed diagnosis of multiple myeloma according to IMWG criteria; • Measurable disease according to the IMWG criteria; • Patients who are either unfit or frail according to the IMWG criteria; • Age 18 years or older. • Absolute neutrophil count (ANC) >= 1.0 x109/l and platelet count >= 75x109/l. Platelet transfusions and G-CSF to help patients meet eligibility criteria are not allowed; • Written informed consent, including consent for additional bone marrow and blood sampling and a skin biopsy • Patient is capable of giving informed consent. • Negative pregnancy test at study entry (only for women of childbearing potential); • Male patients and female patients of childbearing potential must agree to use adequate contraception from the time of signing the informed consent form through 90 days after the last dose of study drug.
Exclusion criteria
Exclusion criteria: • Non-secretory MM; • Plasma cell leukemia; • Systemic Amyloid Light-chain (AL) amyloidosis; • Central nervous system involvement; • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent; • Neuropathy, grade 1 with pain or grade >= 2; • Severe cardiac dysfunction (NYHA classification III-IV); • Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia*s formula (QTcF) >470 msec; • Chronic obstructive pulmonary disease (COPD) with an Forced Expiratory Volume in 1 second (FEV1) = 3 x ULN or transaminases >= 5 times normal level) except patients with Gilbert*s syndrome as defined by > 80% unconjugated bilirubin • Creatinine clearance = 7 days between radiotherapy and administration of ixazomib) or a short course of steroids (e.g. 4 day treatment of dexamethasone 40 mg/day or equivalent) are allowed; • Major surgery within 14 days before enrollment; • Any serious medical or psychiatric illness, or familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule; • Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial; • Female patients who are lactating.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Overall response rate (at least PR) on induction therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Discontinuation rate due to toxicity of maintenance therapy with Ixazomib and daratumumab. • Safety and toxicity as defined by type, frequency and severity of adverse events as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4 • Complete Response and Very Good Partial Response rate after 9 induction cycles and on protocol • Immunophenotypic Complete Response after 9 induction cycles and on protocol • Minimal Residual Disease negative flow cytometry of bone marrow on protocol • PET-CT negative, defined as disappearance of increased tracer uptake at entry, or decrease to less than mediastinal blood pool SUV or decrease to less than surrounding normal tissue • Progression free survival, defined as time from registration to progression or death from any cause, whichever comes first • Overall survival, measured from date of registration to death from any cause. Patients alive at the date last contact, will be censored • Time to (maximum) response • Improvement in response from the start of maintenance therapy • Discontinuation rate due to toxicity of 9 cycles of Ixazomib, daratumumab and low-dose dexamethasone. • Time to next treatment • PFS2, defined as the time from registration to the date of objective disease progression or death from any cause after second line therapy • Quality of life as defined by the EORTC QLQ-C30, QLQ-MY20 and EQ-5D-5L definitions Exploratory endpoints • Geriatric assessments (both questionnaires and physical assessments), senescence markers in fibroblasts obtained by skin biopsy and sarcopenia as determined by CT-scan that reflect biological age and predict feasibility and the toxicity of treatment • Identification of immunological and molecular prognostic markers that predict feasibility and the toxicity of treatment • Identification of biomarkers for response | — |
Countries
Netherlands
Outcome results
None listed