Optimising Renal Outcome in Myeloma Renal Failure

NCT02424851 | Completed Phase 2 Results DMC

• 2 other identifiers: 26866138-MMY20702012-003947-31
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to compare the effectiveness of bortezomib versus thalidomide in reducing free light chains in the blood of myeloma patients. In addition participants will receive bendamustine (chemotherapy) and dexamethasone (steroids), which increase the effectiveness of both bortezomib and thalidomide. The trial will also study whether an earlier reduction of free light chains increases the chances of the kidneys recovering.

Conditions

Multiple Myeloma; Chronic Kidney Disease

Keywords

myeloma; multiple myeloma; chronic kidney disease; renal failure; bortezomib; Velcade; thalidomide; bendamustine; dexamethasone; serum free light chains; proteosomal inhibition; immunomodulatory

Outcome Measures

Primary Outcomes (2)

• Number of Participants With >50% Reduction From Baseline in Serum Free Light Chain

  End of week 6 (after receiving two cycles of therapy)

• Number of Participants With Different Renal Responses to Treatment

  End of week 12 (after receiving 4 cycles of therapy)

Secondary Outcomes (4)

• Haematological and Non-haematological Toxicity in Both Treatment Arms

  End of weeks 3, 6, 9, 12 (after receiving 4 cycles of therapy), 30 days after final treatment and 12 months after randomisation

• Overall Survival

  1 month post end of treatment and 1 year post randomisation

• Renal Response After Two Cycles of Trial Treatment

  End of 2nd treatment cycle, week 6

• Quality of Life Measured by the EQ-5D-3L Questionnaire at Baseline and 1 Month Follow up

  Baseline and 1 month follow up

Study Arms (2)

Arm A (BBD)

ACTIVE COMPARATOR

Bortezomib, Bendamustine and Dexamethasone

Drug: Bortezomib; Drug: Bendamustine; Drug: Dexamethasone

Arm B (BTD)

ACTIVE COMPARATOR

Thalidomide, Bendamustine and Dexamethasone

Drug: Thalidomide; Drug: Bendamustine; Drug: Dexamethasone

Interventions

Bortezomib DRUG

1.3 mg/m2 subcutaneously\* days 1, 4, 8 and 11 of each cycle. Number of cycles: Four 21 day cycles (participants not suitable for ASCT (autologous stem cell transplant) will continue up to 6 cycles on the treatment regimen to which they were randomised). \*intravenous infusion available in case of patient intolerance to subcutaneous bortezomib

Also known as: Velcade

Arm A (BBD)

Thalidomide DRUG

100 mg daily orally, preferably at night, days 1-21 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised)

Arm B (BTD)

Bendamustine DRUG

60 mg/m2 i.v. days 1 and 8 of each cycle. Four 21 day cycles (participants not suitable for ASCT will continue up to 6 cycles on the treatment regimen to which they were randomised)

Arm A (BBD); Arm B (BTD)

Dexamethasone DRUG

40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle

Arm A (BBD); Arm B (BTD)

Eligibility Criteria

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

You may qualify if:

• Participant is willing and able to give informed consent for participation in the trial.
• Patients attending NHS (National Health Service) Haemato-oncology centres.
• Patients with newly diagnosed symptomatic myeloma.
• Glomerular Filtration Rate (GFR) \<30 mls/min.
• Chronic kidney disease (CKD) staging is based on estimated or measured GFR. CKD stage 4 (15-29 ml/min) and CKD stage 5 (\<15 ml/min) are eligible to enter the study. It is expected centres will consider use of fluid resuscitation and pulsed dose of steroid therapy in this group of patients to salvage renal function prior to trial screening.
• A number of patients with newly diagnosed myeloma and renal failure will have a pre-existing medical condition (hypertension, diabetes etc.) causing renal damage. Where there is a medical condition (e.g. hypertension, diabetes) which may cause renal damage, there must have been a further decline (≥15 mls/min GFR) between previous steady state and the study screening.
• Female participants of childbearing potential and male patients whose partner is a woman of childbearing potential must be prepared to use contraception in accordance with (and consent to) the Celgene-approved process for thalidomide and lenalidomide Risk Management and Pregnancy Prevention Programme.
• Women of childbearing potential must have a negative pregnancy test performed by a healthcare professional in accordance with the Celgene-approved process for thalidomide and lenalidomide Risk Management and Pregnancy Prevention.
• Free of prior malignancies for ≥ 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, localised prostate cancer or carcinoma "in-situ" of the cervix or breast.
• In the Investigator's opinion, is able and willing to comply with all trial requirements.
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.

You may not qualify if:

• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial or the female partner of a male participant planning a pregnancy during the course of the trial.
• Known allergy to investigational drugs.
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
• Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \< 1.0 x10\^9/L
• Platelet count \<75 x 10\^9/L
• Serum SGOT/AST or SGPT/ALT (serum glutamic oxaloacetic transaminase/aspartate aminotransferase or serum glutamic pyruvic transaminase/alanine aminotransferase) \>3 x upper limit of normal.
• Use of any standard/experimental anti-myeloma drug therapy excluding dexamethasone 14 days prior to trial entry.
• CKD stages \< 4.
• Intention to use a physical method of serum free light chain removal such as plasma exchange or high cut off dialysis.
• Grade 2 neuropathy or more (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.0) will preclude use of thalidomide and bortezomib.
• Participants who have participated in another research trial involving an investigational product in the past 12 weeks.
• Contraindicated to receive either one of the study drugs, thalidomide, bortezomib, bendamustine based on the respective summary of product characteristics.

Sponsors & Collaborators

• Oxford University Hospitals NHS Trust: lead
• Janssen-Cilag Ltd.: collaborator
• Bloodwise: collaborator
• University of Warwick: collaborator
• University of Birmingham: collaborator

Study Sites (9)

Basingstoke & North Hampshire Hospital

Basingstoke, United Kingdom

Location

Heartlands Hospitals

Birmingham, United Kingdom

Location

Kent & Canterbury Hospital

Canterbury, CT1 3NG, United Kingdom

Location

St Helier Hospital

Epsom, United Kingdom

Location

Royal Liverpool Hospital

Liverpool, United Kingdom

Location

Kings College Hospital

London, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Queen Alexandra Hospital

Portsmouth, United Kingdom

Location

Great Western Hospital

Swindon, United Kingdom

Location

Related Publications (26)

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Related Links

• Cancer Research UK - Myeloma Statistics

MeSH Terms

Conditions

Multiple Myeloma; Renal Insufficiency, Chronic; Neoplasms, Plasma Cell; Renal Insufficiency

Interventions

Bortezomib; Thalidomide; Bendamustine Hydrochloride; Dexamethasone

Condition Hierarchy (Ancestors)

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; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Butyrates; Acids, Acyclic; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Richard Brouwer
• Organization: Oxford University Hospitals NHS Foundation Trust

richard.brouwer@ouh.nhs.uk

441865226950

Study Officials

• Karthik Ramasamy

  National Health Service, United Kingdom

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: March 10, 2015
• First Posted: April 23, 2015
• Study Start: November 1, 2014
• Primary Completion: April 20, 2020
• Study Completion: April 20, 2020
• Last Updated: January 27, 2022
• Results First Posted: January 27, 2022

Record last verified: 2022-01

Locations

GB (9)