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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 September 2015
• Main ID: NCT02545907
• Date of registration: 27/08/2015
• Prospective Registration: Yes
• Primary sponsor: University College, London
• Public title: A Dose Escalation Study of Carfilzomib Taken With Thalidomide and Dexamethasone in Relapsed AL Amyloidosis CATALYST
• Scientific title: A Single Arm Open Labeled Multicentre Phase 1b Dose Escalation Study of Carfilzomib Taken in Combination With Thalidomide and Dexamethasone in Relapsed AL Amyloidosis
• Date of first enrolment: October 2015
• Target sample size: 36
• Recruitment status: Not yet recruiting
• URL: https://clinicaltrials.gov/show/NCT02545907
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1/Phase 2

Countries of recruitment

United Kingdom

Contacts

• Name: Sarah Flynn

• Name: Ashutosh Wechalekar, Dr
• Affiliation: University College London, National Amyloidosis Centre

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Amyloidosis

Intervention(s)

Drug: Dexamethasone

Drug: Thalidomide

Drug: Carfilzomib

Primary Outcome(s)

Number of participants experiencing Grade 3 or 4 toxicity as assessed by CTCAE v4.0. [Time Frame: End of study; 30 months from opening.]

Dose-Limiting Toxicities as assessed by reported data [Time Frame: After 1 cycle of treatment; to be completed within 1 year.]

Secondary Outcome(s)

Number of patients progression-free at 6 months based on reported data. [Time Frame: End of study; 30 months from opening.]

Amyloidotic organ response rate within 3 months and 6 months based on biochemical, electrocardiographical, and radiographical assessment. [Time Frame: End of study; 30 months from opening.]

Number of deaths at 6 months based on reported data. [Time Frame: End of study; 30 months from opening.]

Number of patients withdrawing from treatment based on reported data. [Time Frame: End of study; 30 months from opening.]

Clonal response rate within 3 months, at 3 months, within 6 months and at 6 months as determined by paraprotein and free light chain assessment. [Time Frame: End of study; 30 months from opening.]

Number of patients experiencing dose delays based on reported data. [Time Frame: End of study; 30 months from opening.]

Maximum response determined by paraprotein and free light chain assessment. [Time Frame: End of study; 30 months from opening.]

Compliance profile of KTD based on reported chemotherapy compliance data. [Time Frame: End of study; 30 months from opening.]

Time to maximum response based on reported data. [Time Frame: End of study; 30 months from opening.]

Relative dose intensity based on pharmacokinetic assessments. [Time Frame: End of study; 30 months from opening.]

Time to amyloidotic organ response based on reported data. [Time Frame: End of study; 30 months from opening.]

Secondary ID(s)

14/0786

Source(s) of Monetary Support

Please refer to primary and secondary sponsors