Optimising Renal Outcome in Myeloma Renal Failure
Condition: Multiple Myeloma; Chronic Kidney Disease
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
Intervention: Bortezomib; Thalidomide; Bendamustine; Dexamethasone
Intervention description: 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; 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); 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); 40mg orally days 1-2, 4-5, 8-9 and 11-12 of each cycle
Intervention MeSH terms: Thalidomide; Dexamethasone; Bortezomib; Bendamustine Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: myeloma; multiple myeloma; chronic kidney disease; renal failure; bortezomib; Velcade; thalidomide; bendamustine; dexamethasone; serum free light chains; proteosomal inhibition; immunomodulatory

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.