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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 treatment

Maximum 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

Page last updated: August 23, 2015

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