Specialty: Cancer, Primary sub-specialty: Haematological oncology
Conditions
Interventions
The trial comprises a dose escalation phase and a dose expansion phase. The dose escalation phase will assess the safety and tolerability of various doses of carfilzomib (27 mg/m2, 36 mg/m2, 45 mg/m2,
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18 years or greater 2. Diagnosis of systemic AL amyloidosis with 2.1. Exclusion of genetic mutations associated with hereditary amyloidosis and immunohistochemical exclusion of AA and TTR amyloidosis as appropraite 2.2. Amyloid related organ dysfunction or organ syndrome 3. Measurable clonal disease 4. Clonal relapse after previous chemotherapy or autograft stem cell transplant OR refractory clonal disease to previous chemotherapy or stem cell transplant 5. Capable of providing written, informed consent and willing to follow study protocol 6. Life expectancy =6 months 7. ECOG performance status of 0-2 8. Platelet count =50 x 10(9)/l 9. Neutrophil count =1 x 10(9)/l 10. Haemoglobin =8 g/dl 11. Bilirubin <2 times or alkaline phosphatase <4 times upper limit of normal 12. Female participants of child-bearing potential must have a negative pregnancy test prior to treatment and agree to use dual methods of contraception for the duration of the study and for 30 days following completion of study. Male participants must also agree to use a barrier method of contraception for the duration of the study and for 30 days following completion of study if sexually active with a female of child-bearing potential. Women who could become pregnant must have taken precautions not to become pregnant for 1 month before the start of the study 13. Participants must comply with the Celgene pregnancy prevention programme for thalidomide
Exclusion criteria
Exclusion criteria: 1. Overt symptomatic multiple myeloma 2. Amyloidosis of unknown or non AL type 3. Localised AL amyloidosis (in which amyloid deposits are limited to a typical single organ, for example the bladder or larynx, in association with a clonal proliferative disorder within that organ) 4. Trivial or incidental AL amyloid deposits in the absence of a significant amyloid related organ syndrome (e.g., isolated carpal tunnel syndrome) 5. Refractory to or progressive disease with an IMid and proteasome inhibitor combination 6. Allogeneic stem cell transplantation 7. Solid organ transplantation 8. Severe peripheral or autonomic neuropathy causing significant functional impairment that, in the investigator’s opinion, may interfere with protocol adherence 9. eGFR 0.07 and NT-proBNP >700 pMol/L OR NT-proBNP >1000 pMol/L OR supine SBP <100 mm of Hg 13. Myocardial infarction in the proceeding 6 months or unstable angina or conduction abnormalities uncontrolled by medication or devices 14. Concurrent active malignancies, except surgically removed basal cell carcinoma of the skin or other in situ carcinomas 15. Pregnant, lactating or unwilling to use adequate contraception 16. Systemic infection unless specific anti-infective therapy is employed. 17. Known or suspected HIV infection 18. Contraindication to any of the required concomitant drugs or supportive treatments 19. Any other clinically significant medical disease or condition or psychiatric illness that, in the Investigator’s opinion, may interfere with protocol adherence or a participant’s ability to give informed consent 20. Previous experimental agents within 3 months before the date of registration 21. Known allergies to Carfilzomib, Thalidomide or Dexamethasone
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Dose-Limiting Toxicities (Dose escalation phase), between the time of receiving the first registered dose of carfilzomib in cycle 1 and day 1 cycle 2, in order to establish the Maximum Tolerated Dose (MTD) and recommended dose (RD) of carfilzomib in combination with thalidomide and dexamethasone at the end of the dose escalation phase, as assessed by counting the total number of dose limiting toxicities reported on the case report forms. This will be carried out at the end of the dose escalation phase. 2. Proportion of patients treated who experience any grade 3 or 4 CTCAE toxicity throughout all treatment cycles, will be determined at the end of the dose escalation phase, as assessed by counting the number of patients experiencing any grade 3 or 4 CTCAE toxicity reported on the case report forms. This will be carried out at the end of the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Clonal response rate within 3 months, at 3 months, within 6 months and at 6 months will be assessed by reporting of clonal response rates on case report forms for each patient. This assessment will be compiled and assessed as a whole at the end of the trial. 2. Amyloidotic organ response rate within 3 months and 6 months will be assessed by reporting of organ response rates on case report forms for each patient. This assessment will be compiled and assessed as a whole at the end of the trial. 3. Time to amyloidotic organ response will be assessed by reporting of organ response rates and determining how long it takes for this to happen as reported on case report forms for each patient. This assessment will be compiled and assessed as a whole at the end of the trial. 4. Number of deaths at 6 months will be assessed by counting the number of deaths reported on the case report forms at 6 months. 5. Number of patients progression free at 6 months will be assessed by counting the number of patients who have not progressed reported on the case report forms at 6 months. 6. Maximum response will be assessed by reporting of maximum response rates on case report forms for each patient. This assessment will be compiled and assessed as a whole at the end of the trial. 7. Time to maximum response will be assessed by reporting of maximum response rates and determining how long it takes for this to happen as reported on case report forms for each patient. This assessment will be compiled and assessed as a whole at the end of the trial. 8. Number of patients withdrawing from treatment will be assessed by counting the number of withdrawals reported on the case report forms at the end of the trial. 9. Number of patients experiencing dose delays, and compliance profile of KTD will be assessed by looking at how many patients experience dose delays and how pa | — |
Countries
United Kingdom
Contacts
Public ContactErin Peat
Outcome results
None listed