Condition category
Cancer
Date applied
19/06/2014
Date assigned
19/06/2014
Last edited
03/03/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Dr Karthik Ramasamy

ORCID ID

Contact details

Late Phase Haematology Research Team
Cancer & Haematology Centre
Churchill Hospital Old Road
Headington
Oxford
OX3 7LE
United Kingdom
-
OPTIMAL.trial@nhs.net

Additional identifiers

EudraCT number

2012-003947-31

ClinicalTrials.gov number

NCT02424851

Protocol/serial number

26866138-MMY2070

Study information

Scientific title

A study of Thalidomide, Bendamustine, and Dexamethasone (BTD) vs Bortezomib, Bendamustine, and Dexamethasone (BBD) in patients with renal failure defined as a GFR below 30 ml/min

Acronym

OPTIMAL

Study hypothesis

Renal impairment is a life-threatening complication of myeloma. Up to 20-25% of patients will present at myeloma diagnosis with renal dysfunction.
In this Phase II study, 120 newly diagnosed myeloma patients with eGFR less than 30 ml/min from approximately 20 centres will be randomised to receive either Thalidomide or Bortezomib; all patients will receive bendamustine and dexamethasone in three weekly cycles. All patients will receive a minimum of four cycles.

Aims:
1. Establish whether proteasomal inhibition (bortezomib) or IMiD (thalidomide) based therapy achieves threshold reduction of sFLC in a significant majority of patients
2. Establish whether sFLC response to the first two cycles (early responder) predicts haematological and renal response to the next two cycles of therapy
3. Establish an early time point for assessment of sFLC reduction as a biomarker for response

Ethics approval

Northeast Newcastle and North Tyneside2 (NNT2) Committee, 03/03/2014, ref:13-NE-0361;

Study design

Randomised; Interventional; Design type: Process of Care

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: Cancer; Subtopic: Haematological Oncology; Disease: Myeloma

Intervention

BTD vs BBD, Thalidomide + Bendamustine + Dexamethasone (BTD) vs Bortezomib + Bendamustine + Dexamethasone (BBD); Follow Up Length: 12 month(s); Study Entry: Single Randomisation only

Added 16/02/2017:
Potential eligible participants are screened and baseline assessments undertaken including: medical history; treatment history; concomitant medications; bone imaging; local laboratory evaluations.
Eligible patients are randomised to one of two treatment groups, stratified by age and Chronic Kidney Disease (CKD) stage.

Group 1: Bortezomib, Bendamustine and Dexamethasone (BBD)
Participants receive Bortezomib 1.3 mg/m2 subcutaneous on days 1, 4, 8 and 11. They receive Bendamustine 60 mg/m2 intravenous infusion on days 1 and 8. They also take Dexamethasone 40 mg daily orally on days 1-2,4-5,8-9,11-12.

Group 2: Thalidomide, Bendamustine and Dexamethasone (BTD)
Participants take Thalidomide 100 mg daily p.o. preferably at night for 21 days. They receive Bendamustine 60 mg/m2 intravenous infusion on days 1 and 8. They also take Dexamethasone 40 mg daily orally on days 1-2,4-5,8-9,11-12.

Participants are randomised to receive up to 4 cycles of either Bortezomib (Arm A) or Thalidomide (Arm B) (21 days in each cycle). All participants receive Bendamustine and Dexamethasone as combination therapy. Participants not considered suitable for autologous stem cell transplant (ASCT) may be given a further two cycles of their allocated treatment (up to 6 cycles in total).

During treatment assessments are undertaken including: physical examination; concomitant medications, local laboratory evaluations and adverse event reporting.

All participants who have received at least 2 cycles of their allocated treatment are followed up at 1 month post end of treatment (approximately 30 days after last dose) and 12 months post randomisation. These assessments include physical examination, disease status, treatment efficacy, overall survival and local laboratory evaluations.

Participants are asked to complete a validated (EQ-5D- 3L) Quality of Life questionnaire at screening (baseline), on day 1 of each treatment cycle and at 1 month and 12 month follow-up.

Central laboratory samples are collected at screening (baseline), during treatment and at 1 month follow up and sent to both Oxford and Birmingham.

Intervention type

Drug

Phase

Not Applicable

Drug names

Thalidomide + Bendamustine + Dexamethasone (BTD), Bortezomib + Bendamustine + Dexamethasone (BBD)

Primary outcome measures

Response defined as >50% reduction (from baseline) in sFLC week 6 (end of cycle 2)

Added 16/02/2017:
1. Serum free light chain response is measured as the proportion of participants with response defined as >50% reduction (from baseline) in sFLC week 6 (end of cycle 2).
2. Myeloma response is measured by the renal response (Modified IMWG Uniform Criteria Of Response and Progression) at the end of 4 cycles of therapy

Secondary outcome measures

Renal response at end of four cycles of therapy.

Added 16/02/2017:
1. Overall response and correlation with monoclonal protein the urine is measured by the sFLC response at week 1, 2, 3, 4, 5, 6, 9 and 12
2. Haematological and non-hameatological toxicity in both arms is preasured by haematological responses adverse Events (NCI CTCAE v4.0) criteria
3. Survival at 1 month post end of treatment and 12 months post randomisation
4. change in renal function between the two treatment regimens is assessed by the renal response (defined by the IMWG renal response criteria) at the end of cycle 2 and cycle 4
5. Treatment effects on other patient reported outcomes is measured by the EQ-5D-3L Quality of life questionnaire at baseline, start of each treatment cycle and at 1 and 12 months post follow-up

Overall trial start date

06/06/2014

Overall trial end date

30/10/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients attending NHS haemato-oncology centres
2. Patients with newly diagnosed symptomatic myeloma and renal failure
3. Patients willing and able to give written informed consent
4. Chronic kidney disease stage 4 or 5
5. GFR <30 ml/min
6. 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 (eg. hypertension, diabetes) which may cause renal damage, there must have been a further decline (=15 ml/min) between previous steady state and the study screening
7. Women of childbearing potential (WCBP) and male participants whose partner is a WCBP 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
8. WCBP 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
9. 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
10. In the Investigator's opinion, is able and willing to comply with all trial requirements
11. Willing to allow his or her GP and consultant, if appropriate, to be notified of participation in the trial

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 120; UK Sample Size: 120

Participant exclusion criteria

1. Female patient 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
2. Age <18 years
3. Known allergy to investigational drugs
4. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participant 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
5. Any of the following laboratory abnormalities:
5.1. Absolute neutrophil count (ANC) <1.0 x 10(9)/L
5.2. Platelet count <75 x 10(9)/L
5.3. Serum SGOT/AST or SGPT/ALT >3 x upper limit of normal
6. Use of any standard/experimental anti-myeloma drug therapy 14 days prior to trial entry
7. CKD <4
8. Intention to use a physical method of serum free light chain removal such as plasma exchange or high cut-off dialysis
9. Grade 2 neuropathy (NCICTCAE v 4.0) or more will preclude use of thalidomide and bortezomib
10. Participants who have participated in another research trial involving an investigational product in the past 12 weeks.

Recruitment start date

06/06/2014

Recruitment end date

30/10/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Churchill Hospital, Oxford (lead site)
Oxford University Hospitals NHS Foundation Trust Old Road
Oxford
OX3 7LE
United Kingdom

Trial participating centre

St Helier Hospital
Epsom and St Helier University Hospitals NHS Trust Wrythe Lane Sutton
Carshalton
SM5 1AA
United Kingdom

Trial participating centre

Queen Alexandria Hospital
Portsmouth Hospitals NHS Trust Southwick Hill Road
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

Basingstoke and North Hampshire Hospital
Hampshire Hospitals NHS Foundation Trust Aldermaston Road
Basingstoke
RG24 9NA
United Kingdom

Trial participating centre

Kent and Canterbury Hospital
East Kent Hospitals University NHS Foundation Trust Ethelbert Road Canterbury Kent
Canterbury
CT1 3NG
United Kingdom

Trial participating centre

Royal Liverpool Hospital
Royal Liverpool Hospital and Broadgreen University Hospitals NHS Trust Prescot Street
Liverpool
L7 8XP
United Kingdom

Sponsor information

Organisation

Oxford University Hospitals NHS Foundation Trust

Sponsor details

Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.ouh.nhs.uk/

Funders

Funder type

Charity

Funder name

Bloodwise

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Janssen Cilag International NV

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Final study report and publication planned in a high-impact peer reviewed journal.

IPD sharing plan:
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Intention to publish date

30/10/2019

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

22/02/2017: Basingstoke and North Hampshire Hospital, Kent and Canterbury Hospital and Royal Liverpool Hospital have been added as trial participating centres. 16/02/2017: Overall trial end date was changed from 28/02/2016 to 30/10/2018. Recruitment end date changed from 28/02/2016 to 30/10/2017. Churchill Hospital, St Helier Hospital and Queen Alexandria Hospital as trial participating centres have been added. Changed contact from Elizabeth Ward to Karthik Ramasamy. Please note that NAPP Pharmaceuticals is no longer funding the study and Bloodwise charity (formerly LLR) has funded from the start of this study.