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

NCT02461888 | Completed Phase 2 DMC

• 1 other identifier: HM13/10993
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 18

Brief 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.

Conditions

Multiple Myeloma

Keywords

Relapsed; Refractory; Cyclophosphamide; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  From randomisation to first documented evidence of disease progression or death, up to 36 months.

Secondary Outcomes (10)

• Response to treatment

  From initial trial treatment until at least partial response is achieved, up to 36 months..

• 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.

• Time to progression

  From randomisation to first documented evidence of disease progression, up to 36 months..

• 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.

• Response duration

  From the first observation of at least partial response until disease progression, up to 36 months.

Study Arms (2)

Ixazomib, CD

EXPERIMENTAL

Ixazomib, cyclophosphamide and dexamethasone (ICD) will be administered as part of a 28 days cycle until disease progression, intolerance, toxicity or withdrawal. Dosing schedule: * Ixazomib 4mg orally on days 1, 8 and 15 * Cyclophosphamide 500mg orally on days 1, 8 and 15 * Dexamethasone 40mg orally on days 1-4 and 12-15

Drug: Ixazomib; Drug: Cyclophosphamide; Drug: Dexamethasone

CD

ACTIVE COMPARATOR

Cyclophosphamide and dexamethasone (CD) will be administered as part of a 28 days cycle until disease progression, intolerance, toxicity or withdrawal. Dosing schedule: * Cyclophosphamide 500mg orally on days 1, 8 and 15 * Dexamethasone 40mg orally on days 1-4 and 12-15

Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

Chemotherapy

Ixazomib, CD

Cyclophosphamide DRUG

Chemotherapy

CD; Ixazomib, CD

Dexamethasone DRUG

Chemotherapy

CD; Ixazomib, CD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Leeds: lead
• Myeloma UK: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (18)

Queen Elizabeth Medical Centre

Birmingham, B15 2TH, United Kingdom

Location

Heart of England NHS Foundation Trust

Birmingham, B9 5ST, United Kingdom

Location

Royal Bournemouth General Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

University Hospital Bristol NHS Foundation Trust

Bristol, BS1 3NU, United Kingdom

Location

North Tees and Hartlepool NHS Foundation Trust

Hartlepool, TS24 9AH, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

Royal Liverpool and Broadgreen University Hospital NHS Trust

Liverpool, L7 8XP, United Kingdom

Location

Barts and the London NHS Trust

London, E1 1BB, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

Guy's and St Thomas's NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospital NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S5 7AU, United Kingdom

Location

Southampton University Hospital NHS Trust

Southampton, SO16 6YD, United Kingdom

Location

The Royal Wolverhampton Hospital NHS Trust

Wolverhampton, WV10 0QP, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

ixazomib; Cyclophosphamide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Gordon Cook

  Leeds Teaching Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: June 1, 2015
• First Posted: June 3, 2015
• Study Start: December 1, 2015
• Primary Completion: April 1, 2022
• Study Completion: January 19, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

GB (18)