Phase II Randomised Trial of Cyclophosphamide and Dexamethasone in Combination With Ixazomib in Relapsed or Refractory Multiple Myeloma.
Information source: University of Leeds
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple Myeloma
Intervention: Ixazomib (Drug); Cyclophosphamide (Drug); Dexamethasone (Drug)
Phase: Phase 2
Status: Not yet recruiting
Sponsored by: University of Leeds Official(s) and/or principal investigator(s): Gordon Cook, Principal Investigator, Affiliation: Leeds Teaching Hospitals NHS Trust
Overall contact: Debbie Sherratt, Phone: 0113 343 1477, Ext: 39141, Email: d.sherratt@leeds.ac.uk
Summary
This study evaluates a new treatment combination of ixazomib with cyclophosphamide and
dexamethasone in relapsed or refractory multiple myeloma. Participants will either receive
ixazomib with cyclophosphamide and dexamethasone or cyclophosphamide and dexamethasone
alone.
Clinical Details
Official title: A Randomised Phase II Trial of Cyclophosphamide and Dexamethasone in Combination With Ixazomib in Relapsed or Refractory Multiple Myeloma (RRMM) Patients Who Have Relapsed After Treatment With Thalidomide, Lenalidomide and Bortezomib.
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Progression free survival
Secondary outcome: Response to treatmentMaximum response Time to progression Time to maximum response Response duration Overall survival Evaluate the safety and toxicity as measured by adverse reactions and serious adverse event reporting. Treatment compliance measured by treatment delays and missed treatment doses. Quality of life measured by the completion of EQ-5D and EORTC QLQ-C30 questionnaires Cost effectiveness of treatment assessed by health economic evaluations.
Detailed description:
Cyclophosphamide and dexamethasone are very commonly used in the treatment of multiple
myeloma and are often given with a third drug (e. g. thalidomide, lenalidomide or
bortezomib). The combination of conventional and new drugs has provided benefits in both
overall survival and progression free survival, however there are few treatments available
for patients who have not responded well (refractory) to their previous treatment or who
need further treatment because their myeloma has come back (relapsed). Thus there is a need
for new agents for these patients.
The development of ixazomib provides the opportunity to increase anti-tumour activity
against a wider range of tumour types. Early clinical trials data suggests it has
anti-tumour activity in heavily pre-treated multiple myeloma patients with durable
responses/disease control and is generally well tolerated.
Cyclophosphamide and dexamethasone are both predominantly used in treatment of multiple
myeloma and for patients with relapsed or refractory multiple myelomas (RRMM), who have
relapsed after bortezomib and lenalidomide. Therefore the evaluation of ixazomib in
combination with cyclophosphamide and dexamethasone is the most valuable and practical
option for patients.
The primary end point of this study is progression-free survival (PFS). Secondary end points
include toxicity and safety.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Able to give informed consent and willing to follow study protocol assessments
- Aged 18 years or over
- Participants with confirmed multiple myeloma based on International Myeloma Working
Group (IMWG) criteria, 2009
- Measurable disease
- Participants with relapsed or relapsed refractory myeloma and now require further
treatment following exposure to thalidomide, lenalidomide and bortezomib regardless
of response to these
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
- Required laboratory values within 14 days prior to Randomisation:
- Platelet count ≥50x109/L. Platelet support is permitted within 14 days prior to
Randomisation
- Absolute neutrophil count ≥1. 0 x 109/L
- Haemoglobin > 9 g/dL. Blood support is permitted
- Alanine aminotransferase (ALT) and / or Aspartate aminotransferase (AST) ≤3 x upper
limit of normal
- Creatinine clearance ≥ 30 ml/min (using Cockcroft Gault formula)
- Bilirubin ≤1. 5 x upper limit of normal
- 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
Exclusion Criteria:
- Those with non-measurable disease
- Those with a solitary bone or solitary extramedullary plasmacytoma
- Plasma cell leukaemia
- Prior malignancy other than those treated with curative 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
- Patients who have previously received MLN9708/Ixazomib 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 severity
- 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 serum 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 MLN9708, 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 14 days prior to randomisation
- Disease involving the Central Nervous System
Locations and Contacts
Debbie Sherratt, Phone: 0113 343 1477, Ext: 39141, Email: d.sherratt@leeds.ac.uk
Heart of England NHS Foundation Trust, Birmingham B9 5ST, United Kingdom; Not yet recruiting
Queen Elizabeth Medical Centre, Birmingham B15 2TH, United Kingdom
University Hospital Bristol NHS Foundation Trust, Bristol BS1 3NU, United Kingdom; Not yet recruiting
North Tees and Hartlepool NHS Foundation Trust, Hartlepool TS24 9AH, United Kingdom; Not yet recruiting
Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, United Kingdom; Not yet recruiting
University Hospital of Leicester NHS Trust, Leicester Le5 4QF, United Kingdom; Not yet recruiting
Royal Liverpool and Broadgreen University Hospital NHS Trust, Liverpool L7 8XP, United Kingdom; Not yet recruiting
Barts and the London NHS Trust, London E1 1BB, United Kingdom; Not yet recruiting
Guy's and St Thomas's NHS Foundation Trust, London SE1 9RT, United Kingdom; Not yet recruiting
Imperial College Healthcare NHS Trust, London W2 1NY, United Kingdom; Not yet recruiting
Royal Free Hampstead NHS Trust, London NW3 2QG, United Kingdom; Not yet recruiting
University College London Hospitals NHS Foundation Trust, London NW1 2PG, United Kingdom; Not yet recruiting
The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
Nottingham University Hospital NHS Trust, Nottingham NG7 2UH, United Kingdom; Not yet recruiting
Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S5 7AU, United Kingdom; Not yet recruiting
Southampton University Hospital NHS Trust, Southampton SO16 6YD, United Kingdom; Not yet recruiting
Singleton Hospital, Swansea SA2 8QA, United Kingdom; Not yet recruiting
The Royal Wolverhampton Hospital NHS Trust, Wolverhampton WV10 0QP, United Kingdom; Not yet recruiting
Additional Information
Starting date: July 2015
Last updated: August 4, 2015
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