AL-Amyloidosis MedDRA version: 18.0 Level: LLT Classification code 10024460 Term: Light chain disease myeloma associated System Organ Class: 100000004864
Conditions
Interventions
Product Name: CHX-A"-DTPA-Anti-CD66
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CHX A"-DTPA anti-CD66 antibody
Concentration unit: MBq/kg megabecquerel(s)/kilogram
Concentration
Sponsors
University Southampton Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The main inclusion criteria is patients with systemic AL-amyloidosis with an indication for treatment who satisfy all standard transplant inclusion criteria (good organ function, no significant heart involvement, good performance status). • Aged =18 years. • Have a diagnosis of systemic AL-amyloidosis, either as a new diagnosis or recurrent disease. • Measurable clonal plasma cell dyscrasia. • Amyloid related organ dysfunction or organ syndrome. • Estimated life expectancy of at least 6 months (as defined at trial entry). • Sufficient stem cells for two transplant procedures . • Bone Marrow (BM) cellularity >20%. • Eligible for ASCT in AL amyloidosis defined as fulfilling all of the following criteria : o ECOG Performance Status of 0 or 1 o Cardiac troponin-T =65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: Patients with poor performance, advanced organ involvement or significant cardiac involvement will be excluded from the study. Patients with the following characteristics are ineligible for this study: • Overt symptomatic multiple myeloma. • Amyloidosis of unknown or non AL type. • 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). • Trivial or incidental AL amyloid deposits in the absence of a significant amyloid related organ syndrome (e.g., isolated carpal tunnel syndrome). • NYHA Class III or IV heart failure (appendix 1). • Liver involvement by amyloid causing bilirubin >1.5 times upper limit of normal. • Concurrent active malignancies, except surgically removed basal cell carcinoma of the skin or other in situ carcinomas. • Pregnant, lactating or unwilling to use adequate contraception as listed above • Intolerance / sensitivity to any of the study drugs. • Known positive Human anti-murine antibodies (HAMA). • Unable to provide written informed consent • Involved in another IMP trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This trial is a phase I/IIa study to assess the use of a [90Y]-labelled anti-CD66 as the sole conditioning prior to autologous stem cell transplant conditioning in patients with AL-amyloidosis. The main objective will be to determine the safety and toxicity associated with the use of the [90Y]-labelled anti-CD66 as measured by CTCAE version 4.0 criteria and stem cell engraftment and hence establish the maximum tolerated radiation dose (MTD) over three infused radiation activity levels. ;Secondary Objective: In addition the study will allow the assessment of clonal response (as measured by serial FLC assay) and by using established, validated methods of FLOW cytometry to measure the change in malignant plasma cell population. Disease response, cardiac recovery, time to progression and overall survival will also be reviewed, whilst determining the engraftment status of patients. Finally the study will allow the assessment of the dosimetry model previously developed in Phase I and II trials in this patient group. ;Primary end point(s): Primary objective is: Safety and toxicity of using [90Y]-anti-CD66 as the sole conditioning prior to autologous stem cell transplantation for AL-amyloidosis. Primary Outcome measure is: Specific organ toxicity as defined in CTCAE ver 4.0. Overall number of Serious Adverse Events, Serious Unexpected Adverse Events determined as causally related to the radiolabelled anti-CD66.;Timepoint(s) of evaluation of this end point: at completion of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: at completion of trial;Secondary end point(s): 1. Disease response as determined by changes in the free light chain assay (FLCa) pre and post [90Y]-labelled anti-CD66 and post transplantation. 2. Clonal plasma cell population as determined by FLOW cytometry pre and post transplantation (D100) 3. NT-proBNP levels pre and post (D100) therapy 4. Assessment of TTP and OS. 5. Comparison of organ dosimetry from previous trials using the same antibody vector. 6. Tablation of platelet and neutrophil engraftment. HAMA assay results from samples taken at defined intervals post transplantation | — |
Countries
United Kingdom
Contacts
Public ContactDr Kim Orchard
University Southampton Hospital NHS Trust
Outcome results
None listed