How PHARMExcel Collaborated with ECMC to Deliver a New Revolutionary Radiation Therapy


Study type
Phase I/II
Location UK
Therapeutic area Oncology, Amyloidosis
Product 90Y-anti-CD66 radiolabelled antibody
Sponsor University Hospital Southampton NHS Foundation Trust


"I have found the PHARMExcel team to be efficient, highly professional while being accommodating and very supportive. They are very interactive and excellent in communicating with clinical teams. They have a thorough understanding of the regulatory requirements for managing GCP compliant clinical trials. I have no hesitation in recommending them as a CRO. "

Dr Kim Orchard, Southampton ECMC

About the clinical trial

ECMC logoWorking in partnership with the Experimental Cancer Medicine Centre (ECMC) Network, PHARMExcel lead the phase I clinical trial TRALA (Targeted Radiotherapy for AL-Amyloidosis), researching a new transplant pre-conditioning technique developed by the Targeted Radiotherapy Group at Southampton ECMC, that may result in an improvement in the response rate post-transplant for S-ALA patients.

This complex treatment allows very precise delivery of high radiation doses to the site of disease, in this case the clonal plasma cells, and avoids irradiating healthy organs in compromised individuals.

Why do we need a better treatment for bone marrow cancer?

S-AL-amyloidosis is a serious haematological condition related to multiple myeloma and is characterised by the deposition of AL-amyloid protein fibrils in various organs such as the heart, liver, spleen, and kidneys. The protein is produced by clonal plasma cells present in bone marrow.

Most patients with S-ALA respond to similar treatments used to treat myeloma including high dose chemotherapy and autologous stem cell transplantation which can result in control of their disease and improvement in survival.

AL-A patients, however, are more difficult to treat as they often have additional medical problems such as impaired kidney and cardiac function which can result in significant toxicities associated with high dose chemotherapy.  Even with careful patient selection and screening, the morbidity and mortality associated with autologous stem cell transplantation is much higher than for patients with myeloma.

The benefits of targeted radiotherapy on rare diseases

NHS University Hospital Southampton logo The Targeted Radiotherapy Group at Southampton ECMC developed a technique of preparing patients for transplantation using a radio-labelled monoclonal antibody that targets the bone marrow.

This complex treatment allows very precise delivery of high radiation doses to the site of disease, in this case the clonal plasma cells, and avoids irradiating healthy organs in compromised individuals.


Key facts from the TRALA clinical trial

  • Phase I open label study conducted at five sites in the UK: University Hospital Southampton NHS FT (UHS), Royal Free Hospital NHS FT (RFH), University College Hospital NHS FT London, Royal Victoria Infirmary, Newcastle Hospitals NHS FT and Queen Elizabeth University Hospital Birmingham NHS FT.
  • The study was designed to find the optimal radiation dose that can be delivered safely to patients and to determine if this is associated with a reduction in the production of amyloidogenic protein.
  • Treatment was delivered at Southampton and Royal Free ECMCs only.
  • Patients returned to their home centres for autologous stem cell transplantation (ASCT) after therapy.

PHARMExcel provided full service, CRO support for the trial, including protocol development, study work up, ethics and regulatory approvals, data management, project management, site management and monitoring and safety reporting.

TRALA clinical trial procedure

  • Patients required autologous peripheral blood stem cells to be collected and harvested by standard procedures and cryopreserved, sufficient for two transplant procedures prior to study consent.
  • Patients received an infusion of 111In-anti-CD66 in the department of nuclear medicine in either Southampton or Royal Free Hospitals with gamma camera imaging using whole body planar and SPECT-CT on days 1, 2, 4 and 5.
  • Dosimetry was performed using the scanned images and the estimated absorbed radiation dose to specific organs was calculated using the dosimetry model developed in Southampton. If the dosimetry showed more than two-fold radiation dose to the BM compared to the liver, the patient proceeded to receive the infusion of 90Y-anti-CD66.
  • There were three treatment levels, 1 (30.0MBq/kg), 2 (40.0MBq/kg) and 3 (45.0 MBq/kg), with step-wise increase of the infused 90Y-labelled anti-CD66 (90Y-anti-CD66) radiation activity.
  • Patients were reviewed 7 days after infusion and study samples taken. They were then admitted to their transplant centre usually between days 9 – 11 post 90Y-anti-CD66) when experiencing neutropenia.
  • Autologous stem cells were infused 14 days after 90Y-anti-CD66 in all patients without any additional pre-conditioning chemotherapy.
  • Patients remained in hospital until neutrophil engraftment occurred and they were independent of platelet support.
  • Further reviews were conducted on days 30 and 100 post-transplant.


Outcome of the clinical trial

The group at Southampton has previously shown that very high doses of radiation can be safely delivered to the bone marrow with minimal radiation to other organs. In theory, if radiation could be directed specifically to sites of disease in patients with Systemic-ALA then the benefits of radiation could be used avoiding the unwanted toxicity to normal organs.

The concept behind this study was to explore the use of a novel transplant conditioning agent (90Y-anti-CD66 radiolabelled antibody) in the context of a highly vulnerable patient group and to test the hypothesis that the radiolabelled antibody has disease reduction and efficacy.

If successful, this type of treatment could reduce transplant related morbidity and mortality associated with a standard transplant with high dose chemotherapy.

"The group has shown that very high doses of radiation can be safely delivered to the bone marrow with minimal radiation to other organs. If successful, the results of the study will be used to support a larger Phase II trial expanded to include more ECMCs in the UK."

Dr Kim Orchard, Southampton ECMC

TRALA clinical trial results included:

  • Achieving its primary and all of its secondary end points.
  • Demonstrating the IMP preferentially localised to the bone marrow in all except one (1) patient of the nine (9) patients that passed dosimetry.
  • No Serious Adverse Events (SAEs) or Suspected Unexpected Serious Adverse Reactions (SUSARs) were experienced by patients in any dose cohort.
  • Adverse events were mainly minimal grade 1-2 only.
  • Disease responses were seen in seven (7) patients with two (2) achieving Complete Remission (CR) by Day+100 post-transplant.
  • No patients died within the trial follow-up period of day +100 post-transplant.
  • Overall survival was 100% at day +100 with median follow up of 32.8 months (range 15.3 – 58.4 months) which is excellent for patients with S-ALA undergoing ASCT.

How will this trial influence future treatments?

Liver tissue with amyloidosisThe lack of toxicity, particularly the complete absence of mucositis, but with disease responses would indicate that the 90Y-anti-CD66 could offer an effective treatment option for patients with S-ALA. Several new agents effective in myeloma have shown considerable activity in S-ALA including monoclonal antibodies such as Daratumumab. Although able to induce excellent responses, the majority of patients will relapse. While Autologous Stem Cell Transplant remains an option for S-ALA the use of targeted radiotherapy could play an important role in providing a method of consolidation or for treatment of relapsed/refractory disease with minimal toxicity.

Future trials could explore the use of a standard dose of radiation to the bone marrow. In addition, DNA-damage repair inhibitors could be used to augment the beneficial effect of targeted radiation.


PHARMExcel partnerships are advancing treatments of the future

The TRALA study, funded by Leukaemia and Lymphoma Research (LLR) and the National Amyloidosis Centre (NAC) based at the Royal Free Hospital in London, demonstrates an excellent example of how PHARMExcel supports the innovation and development of new drugs through collaborative partnerships, such as with the ECMC network.

About the ECMC Network

The Experimental Cancer Medicine Centres (ECMC) Network is uniquely placed to help industry develop the cancer drugs of the future, bringing together an unrivalled team of world-leading clinical experts, working collaboratively to deliver early phase clinical trials.

ECMC researchers are world-leading scientists and clinicians who drive the discovery, development and testing of new treatments to combat cancer. The funding supports over 200 staff involved in early phase trials and translational research.

About PHARMExcel

PHARMExcel is an award-winning, full-service Contract Research Organisation (CRO) providing a flexible and innovative approach to clinical trial delivery. The company is recognised for its in-depth knowledge and experience of the clinical research environment, particularly in the UK, and has a network of regulatory and industry associates, allowing it to provide a global reach.

Media Contact
Katie Howe, Head of Marketing
T: +44 (0)20 3642 6654

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