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No longer recruiting (closed or complete)Last updated: 16 September 2025

AFFIRM-AL: This study is evaluating targeted therapy plus standard of care chemotherapy, compared to placebo plus standard of care chemotherapy, in Mayo Stage IV people with light chain (AL) amyloidosisA Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Birtamimab Plus Standard of Care vs. Placebo Plus Standard of Care in Mayo Stage IV Subjects With Light Chain (AL) Amyloidosis

Trial purpose

Medical clipboardCancer treatment

Tumor type

Blood Cancers Haematological

Age

People18+

Trial acronym

AFFIRM-AL

Clinical summary

Summary

Eligible participants will be randomly allocated to one of two treatment arms.

In the Experimental Arm, participants will receive birtamimab targeted therapy plus standard of care chemotherapy.

Birtamimab will be administered intravenously every 28 days. Standard of care chemotherapy will be a bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone) according to the institutional standard of care. Initiation of daratumumab at randomisation allowed at the discretion of the investigator. 

In the Placebo Comparator Arm, participants will receive placebo plus standard of care chemotherapy.

A saline placebo will be administered intravenously every 28 days. Similar to the Experimental Arm, standard of care chemotherapy will be a bortezomib-containing chemotherapy regimen according to the institutional standard of care. Initiation of daratumumab at randomisation allowed at the discretion of the investigator. 

Conditions

This trial is treating people with light chain amyloidosis

Eligibility

Inclusion

  • Aged ≥18 years and legal age of consent according to local regulations
  • Newly diagnosed and AL amyloidosis treatment-naïve with cardiac involvement
  • Confirmed diagnosis of AL amyloidosis
  • Confirmed Mayo Stage IV AL Amyloidosis as defined by NT-proBNP ≥1800 pg/mL and Troponin-T ≥0.025 ng/mL or high sensitivity cardiac troponin T≥40ng/L and dFLC ≥18 mg/dL
  • Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly.

Exclusion

  • Non-AL amyloidosis.
  • NT-proBNP >8500 pg/mL.
  • Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma except for malignancy biomarker of involved/uninvolved serum free light chain ratio ≥100
  • Subject is eligible for and plans to undergo ASCT or organ transplant during the study.
  • Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit.
  • Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease.
  • ECG evidence of acute ischemia or active conduction system abnormalities
  • Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1.
  • Prior radiotherapy within 4 weeks of Month 1-Day 1.
  • Prior treatment with plasma cell-directed chemotherapy, birtamimab, daratumumab, 11- 1F4, anti-serum amyloid P antibody, doxycycline for amyloid, or other investigational treatment directed at amyloid .
  • Waldenström's macroglobulinemia and/or immunoglobulin M monoclonal gammopathy

Inclusion

  • You have been diagnosed with cancer, but have not received any treatment.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Prothena Biosciences Ltd.

Scientific Title

A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Birtamimab Plus Standard of Care vs. Placebo Plus Standard of Care in Mayo Stage IV Subjects With Light Chain (AL) Amyloidosis

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