Cyclophosphamide and Dexamethasone in combination with Ixazomib (ICD), in relpased or refractory multiple myeloma patients.

• Conditions: Relasped and Refractory Mulitple Myeloma; MedDRA version: 18.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-004511-36-GB
• Lead Sponsor: niversity Of Leeds

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-08-04
• Last Update Posted: 16 November 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

•Able to give informed consent and willing to follow study protocol assessments
•Aged 18 years or over
•Participants with confirmed MM based on IMWG criteria, 2009
•Measurable disease with at least one of the following: 1.Paraprotein >5g/L or 0.5 g/l for IgD subtype; 2.Serum free light chains >100mg/L with abnormal radio for light chain only myeloma; 3.Bence Jones protein >200mg/L
•Participants with relapsed or relapsed refractory myeloma and now require further treatment following exposure to thalidomide, lenalidomide and bortezomib regardless of response to these.
•ECOG Performance Status = 2
•Required laboratory values within 14 days prior to Randomisation:
-Platelet count =50x109/L. Platelet count of 30-50 is acceptable if bone marrow aspirate shows tumour replacement of >50%. Platelet support is permitted within 14 days prior to randomisation although platelet transfusions to help patients meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility
-Absolute neutrophil count =1.0 x 109/L. Growth factor support is not permitted within 14 days prior to randomisation
-Haemoglobin > 9 g/dL. Blood support is permitted
-ALT and / or AST =3 x upper limit of normal
-Creatinine clearance = 30 ml/min (using Cockcroft Gault formula)
-Bilirubin =1.5 x upper limit of normal
•Female participants should avoid becoming pregnant and male participants should avoid impregnating a female partner. Both non-sterilised and sterilised females and males of reproductive age should use effective methods of contraception during the entire trial treatment (including treatment breaks) and up to 90 days after the last dose of trial treatment.
•Post allograft patients may be included if >12 months from transplant.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125

Exclusion Criteria

•Those with non-measurable disease, a solitary bone or solitary extramedullary plasmacytoma, Plasma cell leukaemia
• Prior malignancy other than those treated with surgery.
• Participants with a known or underlying uncontrolled concurrent illness that, in the investigators opinion, would make the administration of the study drug hazardous or circumstances that could limit compliance with the study, including, but not limited to the following: acute or chronic graft versus host disease, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within past 6 months, uncontrolled cardiac arrhythmia, renal failure, psychiatric or social conditions that may interfere with participant compliance, or any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the participant at unacceptable risk for adverse outcome if he/she were to participate in the study.
• Patients who have previously received Ixazomib or MLN9708 in a trial. Previous experimental agents or approved anti-tumour treatment within 30 days before the date of randomisation.
• A maximum of 160mg of dexamethasone (in 40mg blocks) may be given between screening and the beginning of treatment if medically required but should be stopped before trial treatment starts. Bisphosphonates for bone disease and radiotherapy for palliative intent are also permitted.
• Participants with a history of a refractory nausea, diarrhoea, vomiting, malabsorption, gastrointestinal surgery or other procedures that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the study drug(s)
• Peripheral neuropathy of = grade 2 (or grade 1 with pain) severity (as per NCI-CTCAEv4.0)
• Gastrointestinal disorders that may interfere with absorption of the study drug
• Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B or C) hepatitis
• Female patients who are lactating or have a positive pregnancy test during the screening period
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
• Systemic treatment, within 14 days before the first dose of Ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort
• Major surgery within 14 days prior to the date of randomisation
• Radiotherapy within 7 days for palliative pain control or therapeutic radiotherapy within 14 days prior to randomisation.
• Myeloma involving the Central Nervous System.

Study & Design

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