E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myeloma and renal impairment |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of bone marrow, kidney disfunction |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024460 |
E.1.2 | Term | Light chain disease myeloma associated |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives is to compare the amount of serum free light chain circulating in the body, the rate of renal recovery and overall survival in response to two cycles of therapy with either thalidomide or bortezomib in patients presenting with myeloma and renal failure.
The co-primary objective is to determine if the response to treatment of the myeloma tumour burden is mirrored in the renal response at the end of cycle 4. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are as follows:
- Assess whether it is possible to predict how well a participant will respond to either treatment after only two cycles of treatment .
- Compare change in participant's kidney function at the end of cycles 2 and 4 between the two groups.
- Compare participant survival from date of randomisation to end the of treatment (maximum 18 weeks + end of trial visit)
- Compare how well participants tolerate treatments between the two arms of the trial
- Assess participants Quality of life (EQ-5D)before, during and following treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <30mls/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 (≥15mls/min) between previous steady state and the study screening 7.Female 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. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 10-14 days and again within 24 hours of starting study drug. 9. Free of prior malignancies for ≥ 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, 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 |
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E.4 | Principal exclusion criteria |
1. Female patient who is pregnance, 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 serious medical condition 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: - Absolute neutrophil count (ANC) <1.0 x 10(9)/L - Platelet count <75 x 10(9)/L - Serum SGOT/AST or SGPT/ALT >3.0 x upper limit of normal 5. Use of any standard/experimental anti-myeloma drug therapy 14 days prior to trial entry 6. CKD <4 7. Intention to use a physical method of serum free light chain removal such as plasma exchange or high cut off dialysis 8. Grade 2 neuropathy or more will preclude use of thalidomide and bortezomib 9. Participants who have participated in another research trial involving an investigational product in the past 12 weeks. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants with response defined as >50% reduction in sFLC after receiving two cycles of therapy (0- 6 weeks from entry)
Renal response at end of 4 cycles of therapy. Modified IMWG Uniform Criteria Of Response and Progression 1998, 2006, 2011
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Response at 6 weeks and 12 weeks |
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E.5.2 | Secondary end point(s) |
The secondary objectives are as follows: - Assess whether early response can predict individual patient responses at 1, 2, 3, 5, 6, 8, 9, 11 and 12 weeks - Compare change in renal function at the end of cycles 2 and 4 - Assess haematological and non-haematological toxicity in both treatment arms - Compare survival from date of randomisation to end of treatment (12 weeks) - Quality of life (EQ-5D)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
responses at 1, 2, 3, 5, 6, 8, 9, 11 and 12 weeks
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 19 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject (LVLS) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 27 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 27 |