Efficacy and tolerability of ixazomib, daratumumab and low dose dexamethasone (IDd) followed by ixazomib and daratumumab maintenance therapy until progression for a maximum of 2 years in unfit and frail newly diagnosed multiple myeloma patients; an open-label phase II trial
- Conditions
- Multiple Myeloma10035227
- Registration Number
- NL-OMON53051
- Lead Sponsor
- HOVO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 112
• 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.
• 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) < 50% of predicted normal. ;
• Moderate or severe persistent asthma within the past 2 years or currently
uncontrolled asthma of any classification..
• Significant hepatic dysfunction (total bilirubin >= 3 x ULN or transaminases >=
5 times normal level) except patients with Gilbert*s syndrome as defined by >
80% unconjugated bilirubin
• Creatinine clearance <20 ml/min or Calculated Glomerular Filtration Rate
[ml/min/1.73m2] <20;
• Patients with active, uncontrolled infections;
• Patients known to be Human Immunodeficiency Virus (HIV)-positive;
• Patients seropositive for hepatitis B, defined by a positive test for
hepatitis B surface antigen [HBsAg]. Patients with resolved infection (ie,
subjects who are HBsAg negative but positive for antibodies to hepatitis B core
antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs])
must be screened using real-time polymerase chain reaction (PCR) measurement of
hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be
excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV
vaccination (anti-HBs positivity as the only serologic marker) AND a known
history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Patients seropositive for hepatitis C (except in the setting of a sustained
virologic response [SVR], defined as aviremia at least 12 weeks after
completion of antiviral therapy).
• Known GI disease or GI procedure that could interfere with the oral
absorption or tolerance of ixazomib including difficulty swallowing;
• Active malignancy other than MM requiring treatment or a malignancy that has
been treated with chemotherapy currently affecting bone marrow capacity;
• Systemic treatment, within 14 days before the first dose of ixazomib, with
strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine,
phenytoin, phenobarbital), or use of St. John*s wort;
• Pre-treatment with cytostatic drug, immunomodulatory drugs (IMiDs) or
proteasome inhibitors. Radiotherapy (provided the involved field is small and
there are >= 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Overall response rate (at least PR) on induction therapy. </p><br>
- Secondary Outcome Measures
Name Time Method