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Multiple MyelomaPhase 2OPTIMALNCT02424851

Optimising Renal Outcome in Myeloma Renal Failure

A Phase 2 study testing Bortezomib, Thalidomide and Bendamustine in people with Multiple Myeloma and Chronic Kidney Disease, run by Oxford University Hospitals NHS Trust at 9 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma, Chronic Kidney Disease
What is being tested?
Bortezomib, Thalidomide and Bendamustine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
9 sitesUnited Kingdom
Study dates
Nov 2014to 20 Apr 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United Kingdom9 sites

  • Basingstoke & North Hampshire Hospital

    Basingstoke

  • Heartlands Hospitals

    Birmingham

  • Kent & Canterbury Hospital

    Canterbury, CT1 3NG

  • St Helier Hospital

    Epsom

  • Royal Liverpool Hospital

    Liverpool

  • Kings College Hospital

    London

  • Churchill Hospital

    Oxford, OX3 7LE

  • Queen Alexandra Hospital

    Portsmouth

  • Great Western Hospital

    Swindon

Other trials in United Kingdom

About this study

Official title: A Study of Thalidomide, Bendamustine and Dexamethasone (BTD) Versus Bortezomib, Bendamustine and Dexamethasone (BBD) in Patients With Renal Failure Defined as a GFR Below 30 Mls/Min

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.

Read the detailed description

Renal impairment is a life threatening condition of myeloma. 20-25% of patients will present at diagnosis with renal dysfunction. Outcome is poor due to high early mortality, with 28% of newly diagnosed myeloma patients in myeloma trials with renal failure not surviving beyond 100 days, compared with 10% overall.

This study aims to establish:

  1. Whether proteosomal inhibition (bortezomib) or immunomodulatory (thalidomide) based therapy achieves threshold reduction of serum free light chains (sFLCs) in a significant majority of patients.
  2. Whether sFLC response to the first 2 cycles (early responder) predicts haematological and renal response to the next 2 cycles of therapy.
  3. An early time point for assessment of sFLC reduction as a biomarker for response.

Participants will be stratified by age and chronic kidney disease (CKD) stage to receive either bortezomib, bendamustine and dexamethasone (BBD) or thalidomide, bendamustine and dexamethasone (BTD).

Keywords
myeloma, multiple myeloma, chronic kidney disease, renal failure, bortezomib, Velcade, thalidomide, bendamustine, dexamethasone, serum free light chains, proteosomal inhibition, immunomodulatory
Medical subject headings
Multiple Myeloma, Renal Insufficiency, Chronic, Neoplasms, Plasma Cell, Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BortezomibDrug

    Also called Velcade

    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

  • ThalidomideDrug

    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)

  • BendamustineDrug

    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)

  • DexamethasoneDrug

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

Study groups in NCT02424851
Study groupRoleWhat they receive
Arm A (BBD)Active comparatorBortezomib, Bendamustine and Dexamethasone
Receives: Drug: Bortezomib; Drug: Bendamustine; Drug: Dexamethasone
Arm B (BTD)Active comparatorThalidomide, Bendamustine and Dexamethasone
Receives: Drug: Thalidomide; Drug: Bendamustine; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

  2. Number of Participants With Different Renal Responses to Treatment

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

Secondary outcomes (4)

  1. Haematological and Non-haematological Toxicity in Both Treatment Arms

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

  2. Overall Survival

    Measured: 1 month post end of treatment and 1 year post randomisation

  3. Renal Response After Two Cycles of Trial Treatment

    Measured: End of 2nd treatment cycle, week 6

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

    The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is scored on a scale of 1 to 3: 1 (no problems), 2 (some problems), and 3 (extreme problems). Higher score equates to a worse outcome.

    As stated in the official EQ-5D user guide, patient responses to the 5 questions were converted into a single index value as per Dolan P (1997). Modeling valuations for EuroQol health states. Med Care 35(11):1095-108. These index values, with country specific value sets, facilitate the calculation of quality-adjusted life years (QALYs) that are used to inform economic evaluations of health care interventions. In the UK, the values range from -0.594 to +1.

    Measured: Baseline and 1 month follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2015 (estimated)
  2. Study startNov 2014
  3. Primary completion20 Apr 2020
  4. Study completion20 Apr 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02424851
Sponsor's protocol ID
26866138-MMY2070
Other IDs
2012-003947-31
Acronym
OPTIMAL
Status last verified
Jan 2022
First submitted
10 Mar 2015
Last updated
27 Jan 2022
Data monitoring committee
Yes

Publications

  • Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129. Epub 2007 Nov 1.

    PubMed 17975015

  • Brenner H, Gondos A, Pulte D. Expected long-term survival of patients diagnosed with multiple myeloma in 2006-2010. Haematologica. 2009 Feb;94(2):270-5. doi: 10.3324/haematol.13782. Epub 2009 Jan 14.

    PubMed 19144659

  • Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, Dispenzieri A, Kumar S, Clark RJ, Baris D, Hoover R, Rajkumar SV. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009 May 28;113(22):5412-7. doi: 10.1182/blood-2008-12-194241. Epub 2009 Jan 29.

    PubMed 19179464

  • Knudsen LM, Hippe E, Hjorth M, Holmberg E, Westin J. Renal function in newly diagnosed multiple myeloma--a demographic study of 1353 patients. The Nordic Myeloma Study Group. Eur J Haematol. 1994 Oct;53(4):207-12. doi: 10.1111/j.1600-0609.1994.tb00190.x.

    PubMed 7957804

  • Eleutherakis-Papaiakovou V, Bamias A, Gika D, Simeonidis A, Pouli A, Anagnostopoulos A, Michali E, Economopoulos T, Zervas K, Dimopoulos MA; Greek Myeloma Study Group. Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymphoma. 2007 Feb;48(2):337-41. doi: 10.1080/10428190601126602.

    PubMed 17325894

  • Clark AD, Shetty A, Soutar R. Renal failure and multiple myeloma: pathogenesis and treatment of renal failure and management of underlying myeloma. Blood Rev. 1999 Jun;13(2):79-90. doi: 10.1016/s0268-960x(99)90014-0.

    PubMed 10414944

  • Drayson M, Begum G, Basu S, Makkuni S, Dunn J, Barth N, Child JA. Effects of paraprotein heavy and light chain types and free light chain load on survival in myeloma: an analysis of patients receiving conventional-dose chemotherapy in Medical Research Council UK multiple myeloma trials. Blood. 2006 Sep 15;108(6):2013-9. doi: 10.1182/blood-2006-03-008953. Epub 2006 May 25.

    PubMed 16728700

  • Morgan GJ, Davies FE, Gregory WM, Bell SE, Szubert AJ, Navarro Coy N, Cook G, Feyler S, Johnson PR, Rudin C, Drayson MT, Owen RG, Ross FM, Russell NH, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Studies Group. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012 Mar;97(3):442-50. doi: 10.3324/haematol.2011.043372. Epub 2011 Nov 4.

    PubMed 22058209

  • Augustson BM, Begum G, Dunn JA, Barth NJ, Davies F, Morgan G, Behrens J, Smith A, Child JA, Drayson MT. Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United kingdom Medical Research Council trials between 1980 and 2002--Medical Research Council Adult Leukaemia Working Party. J Clin Oncol. 2005 Dec 20;23(36):9219-26. doi: 10.1200/JCO.2005.03.2086. Epub 2005 Nov 7.

    PubMed 16275935

  • Torra R, Blade J, Cases A, Lopez-Pedret J, Montserrat E, Rozman C, Revert L. Patients with multiple myeloma requiring long-term dialysis: presenting features, response to therapy, and outcome in a series of 20 cases. Br J Haematol. 1995 Dec;91(4):854-9. doi: 10.1111/j.1365-2141.1995.tb05400.x.

    PubMed 8547129

  • Kastritis E, Anagnostopoulos A, Roussou M, Gika D, Matsouka C, Barmparousi D, Grapsa I, Psimenou E, Bamias A, Dimopoulos MA. Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethasone-containing regimens and the impact of novel agents. Haematologica. 2007 Apr;92(4):546-9. doi: 10.3324/haematol.10759.

    PubMed 17488666

  • Knudsen LM, Hjorth M, Hippe E. Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol. 2000 Sep;65(3):175-81. doi: 10.1034/j.1600-0609.2000.90221.x.

    PubMed 11007053

  • Alexanian R, Barlogie B, Dixon D. Renal failure in multiple myeloma. Pathogenesis and prognostic implications. Arch Intern Med. 1990 Aug;150(8):1693-5.

    PubMed 2383164

  • Gandhi V. Metabolism and mechanisms of action of bendamustine: rationales for combination therapies. Semin Oncol. 2002 Aug;29(4 Suppl 13):4-11. doi: 10.1053/sonc.2002.34872.

    PubMed 12170425

  • Gaul L, Mandl-Weber S, Baumann P, Emmerich B, Schmidmaier R. Bendamustine induces G2 cell cycle arrest and apoptosis in myeloma cells: the role of ATM-Chk2-Cdc25A and ATM-p53-p21-pathways. J Cancer Res Clin Oncol. 2008 Feb;134(2):245-53. doi: 10.1007/s00432-007-0278-x. Epub 2007 Jul 25.

    PubMed 17653574

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bortezomib, Thalidomide and Bendamustine in people with Multiple Myeloma and Chronic Kidney Disease, run by Oxford University Hospitals NHS Trust at 9 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With >50% Reduction From Baseline in Serum Free Light Chain (time frame: End of week 6 (after receiving two cycles of therapy)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02424851, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2022.

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