Targeted radiotherapy for AL amyloidosis (TRALA)

A phase 1/2a study assessing the use of targeted radiotherapy with Yttrium 90Y-labelled anti-CD 66 as the sole conditioning prior to autologous stem cell transplant in patients with AL amyloidosis.

Background

The most effective treatment available for AL amyloidosis is high dose chemotherapy which kills the abnormal cells in the bone marrow. This treatment is also toxic to the normal bone marrow cells, so patients who receive high dose chemotherapy need to undergo autologous stem cell transplantation, where normal bone marrow cells are collected from the patient before chemotherapy then reinfused after chemotherapy.

This treatment can be very effective, but the high dose chemotherapy may be associated with serious adverse effects. The TRALA study will investigate the use of targeted radiotherapy to destroy the bone marrow cells instead of high dose chemotherapy. Patients will undergo stem cell transplantation, as with high dose chemotherapy. It is hoped that the targeted radiotherapy will be as effective as high dose chemotherapy in destroying the abnormal bone marrow cells that cause AL amyloidosis, with less severe side effects.  Targeted radiotherapy means that the radiation is given directly to the bone marrow using a radiolabelled antibody. This avoids exposure of healthy organs to radiation.

What the trial involves for patients

In order to assess the safety and toxicity associated with use of [90Y] –labelled anti-CD 66 to treat AL amyloidosis and to determine the optimal radiation dose that can be delivered safely to patients with AL amyloidosis, patients will undergo:

  • An initial dosimetry and imaging hospital visit to determine the radiation dose that will be given. This visit will involve administration of a different radiolabelled drug (CD66 radiolabelled with Indium-111), followed by scans 1, 3 and 4 days later.
  • About 1 week later, harvesting of the patient’s stem cells followed by administration of the study treatment with [90Y]-labelled anti-CD 66, then subsequent re-infusion of the patient’s stem cells (autologous stem cell transplantation).
  • Examination and testing by the study doctors 30 days and 100 days after stem cell transplantation.

There will be three treatment levels with step-wise increase of the infused [90Y]-labelled anti-CD66 radiation activity which will be given prior to autologous stem cell transplantation. The total number of participants planned is between 12-18.

Who can take part in the trial

Patients with systemic AL amyloidosis with an indication for treatment who satisfy all standard autologous stem cell transplantation inclusion criteria (good organ function, no significant heart involvement, good performance status).

Outcomes

The primary outcomes assessed in this trial will be the safety and toxicity associated with the use of [90Y]-labelled anti-CD66 and establishment of the maximum tolerated radiation dose (MTD) over three infused radiation activity levels. Other outcomes assessed (secondary outcomes) will include assessment of clonal response, disease response, cardiac recovery, time to progression and overall survival.

Timing

This study is open for recruitment at the NAC.