Phase II Randomised Trial of Cyclophosphamide and Dexamethasone in Combination With Ixazomib in Relapsed or Refractory Multiple Myeloma.

Multiple Myeloma Clinical Trial

— MUKEight  

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02461888
• Other study ID #: HM13/10993
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 2015
• Est. completion date: January 2021

Study information

• Verified date: January 2020
• Source: University of Leeds
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: January 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Ixazomib
Chemotherapy
• Cyclophosphamide
Chemotherapy
• Dexamethasone
Chemotherapy

Locations

Country	Name	City	State
United Kingdom	Heart of England NHS Foundation Trust	Birmingham
United Kingdom	Queen Elizabeth Medical Centre	Birmingham
United Kingdom	Royal Bournemouth General Hospital	Bournemouth
United Kingdom	University Hospital Bristol NHS Foundation Trust	Bristol
United Kingdom	North Tees and Hartlepool NHS Foundation Trust	Hartlepool
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Royal Liverpool and Broadgreen University Hospital NHS Trust	Liverpool
United Kingdom	Barts and the London NHS Trust	London
United Kingdom	Guy's and St Thomas's NHS Foundation Trust	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Royal Marsden Hospital	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Nottingham University Hospital NHS Trust	Nottingham
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	Southampton University Hospital NHS Trust	Southampton
United Kingdom	The Royal Wolverhampton Hospital NHS Trust	Wolverhampton

Sponsors (3)

Lead Sponsor	Collaborator
University of Leeds	Millennium Pharmaceuticals, Inc., Myeloma UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		From randomisation to first documented evidence of disease progression or death, up to 36 months.
Secondary	Response to treatment		From initial trial treatment until at least partial response is achieved, up to 36 months..
Secondary	Maximum response		From initial trial treatment each of the response categories are achieved stringent complete response, complete response, very good partial response, partial response, minimal response or stable disease, up to 36 months.
Secondary	Time to progression		From randomisation to first documented evidence of disease progression, up to 36 months..
Secondary	Time to maximum response		From randomisation until the participant achieves any of the categories stringent complete response, complete response, very good partial response, partial response, minimal response or stable disease, up to 36 months.
Secondary	Response duration		From the first observation of at least partial response until disease progression, up to 36 months.
Secondary	Overall survival		From randomisation to death, up to 36 months.
Secondary	Evaluate the safety and toxicity as measured by adverse reactions and serious adverse event reporting.		From consent until 28 days after the last dose of trial treatment, up to 36 months.
Secondary	Treatment compliance measured by treatment delays and missed treatment doses.		From initial treatment received as per protocol until withdrawal from treatment, up to 36 months.
Secondary	Quality of life measured by the completion of EQ-5D and EORTC QLQ-C30 questionnaires		Completed every 3 months from consent until disease progression, up to 36 months.
Secondary	Cost effectiveness of treatment assessed by health economic evaluations.		From consent up to 36 months.