A Dose Escalation Study of Carfilzomib Taken With Thalidomide and Dexamethasone in Relapsed AL Amyloidosis

• Status: Completed
• Trial end date: 2019-10-21
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluates the safety and efficacy of carfilzomib used in combination with thalidomide and dexamethasone in patients with relapsed AL amyloidosis. The trial begins with a dose escalation phase, in which the maximum tolerated and recommended dose will be determined. The trial will then open into an expansion phase in which the combination efficacy is assessed.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University College, London
• Treatments: BB 1101; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Thalidomide

Criteria

Inclusion Criteria:

• Patients with the following characteristics are eligible for this study:

1. Aged 18 years or greater

2. Diagnosis of systemic AL amyloidosis with:

• exclusion of genetic mutations associated with hereditary amyloidosis and immunohistochemical exclusion of AA and TTR amyloidosis as appropriate.

• Amyloid related organ dysfunction or organ syndrome

3. Measurable clonal disease

4. Clonal relapse after previous chemotherapy or 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 <3

8. Platelet count ≥ 50x109/l)

9. Neutrophil count ≥ 1x109/l)

10. Haemoglobin ≥ 8g/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. Participants must comply with the Celgene pregnancy prevention programme for thalidomide

Exclusion Criteria:

• Patients with the following characteristics are ineligible for this study:

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.

9. eGFR <20ml/min

10. Ejection fraction < 40% or NYHA class III or IV heart failure or uncontrolled hypertension

11. Pulmonary Hypertension

12. Advanced Mayo stage III disease as defined by hs-Troponin T>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 preceeding 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. 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

19. Previous experimental agents or approved anti-tumour treatment within 3 months before the date of registration

20. Known allergies to the IMPs