CATALYST

Background

The most effective treatment available for AL amyloidosis is high dose chemotherapy followed by autologous stem cell transplantation (ASCT). However, this treatment is only appropriate for patients with limited organ involvement, younger age, and good functional status. Most patients with AL amyloidosis are not candidates for ASCT and are treated with combination chemotherapy, often including bortezomib, a proteasome inhibitor. Bortezomib is particularly effective in AL amyloidosis but may have severe side effects. Carfilzomib, a different drug from the proteasome inhibitor class, appears to be better tolerated than bortezomib, with fewer side effects. However, information on carfilzomib in AL amyloidosis treatment is limited. The CATALYST study will investigate safety, efficacy, and dosing of carfilzomib in patients with AL amyloidosis.

The trial

This is a phase 1/1a dose escalation study to investigate safety and efficacy of carfilzomib in combination with thalidomide and dexamethasone, in patients with relapsed or refractory AL amyloidosis. The trial starts with a dose escalation phase to determine maximum tolerated and recommended dose. There will then be an expansion phase to assess efficacy.

What the trial involves for patients

Participants in the escalation phase will receive up to six cycles of treatment with carfilzomib thalidomide and dexamethasone in combination. Carfilzomib will be administered on day 1, 8, and 15, with four groups of patients each receiving different doses of carfilzomib. Following determination of the maximum tolerated dose and recommended dose, the trial will be opened to an expansion phase where participants will receive the recommended dose of carfilzomib, along with thalidomide and dexamethasone. Patients will initially undergo screening assessments at the National Amyloidosis Centre, including a physical examination, laboratory tests, a pregnancy test, an echocardiogram, a 24-hour Holter monitor test, a bone marrow examination (if the doctors think this is necessary), and an assessment of medical history. They will then be referred to their local participating hospital, where some of these assessments will be repeated. If the patient can go on to the trial, they will need to visit their local participating hospital on days 1, 8, and 15 of each 28-day cycle for up to 6 cycles of treatment. At every treatment visit, patients will have blood tests, and at the end of cycle 2, another echocardiogram. During the study, patients will also undergo further assessment sessions at the National Amyloidosis Centre.

Who can take part in the trial

Patients with systemic AL amyloidosis with relapsed or refractory disease after chemotherapy or ASCT.

Primary outcomes

• Assessment of dose-limiting toxicities to establish the maximum tolerated dose of carfilzomib.
• Determination of proportion of patients receiving carfilzomib who experience severe (Grade 3/4) toxicity.

Secondary outcome measures include clonal response rates after 3 and 6 months and organ response rate.

Timing

The study is ongoing at the NAC.