Treatment of unfit and frail newly diagnosed multiple myeloma patients with ixazomib, daratumumab and low dose dexamethasone (IDd) followed by ixazomib and daratumumab maintenance therapy until progression for a maximum of 2 years in .How effective is this treatment and how well is it tolerated?

Phase 1

• Conditions: Multiple Myeloma; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002600-90-BE
• Lead Sponsor: HOVON Foundation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-09-21
• Last Update Posted: 8 March 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 132

Inclusion Criteria

• Previously untreated patients with a confirmed diagnosis of multiple myeloma according to IMWG criteria;
• Measurable disease according to the IMWG criteria ;
(If plasmacytoma is the only measurable parameter, the patient is not allowed to be included in the study, because of difficult response evaluation).
• 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consent for additional bone marrow and blood sampling and a skin biopsy (with the understanding that consent may be withdrawn by the patient at any time without consequences to future medical care).
• 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 (see section 9.4 for details).

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 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 127

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) < 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal;
• Moderate or severe persistent asthma within the past 2 years or currently uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study);
• 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified