A Phase I/IIa (early phase) Study of Targeted Radiotherapy alone for Stem Cell Transplant Conditioning in Systemic AL Amyloidosis

• Register: EUCTR
• Last refreshed on: 18 April 2016
• Main ID: EUCTR2015-002231-18-GB
• Date of registration: 23/09/2015
• Prospective Registration: Yes
• Primary sponsor: University Southampton Hospital NHS Foundation Trust
• Public title: A Phase I/IIa (early phase) Study of Targeted Radiotherapy alone for Stem Cell Transplant Conditioning in Systemic AL Amyloidosis
• Scientific title: A Phase I/IIa Study of Targeted Radiotherapy alone for Stem Cell Transplant Conditioning in Systemic AL Amyloidosis - Targeted Radiotherapy for AL-Amyloidosis –‘TRALA’
• Date of first enrolment: 01/12/2015
• Target sample size: 18
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002231-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

United Kingdom

Contacts

• Name: Dr Kim Orchard
• Affiliation: University Southampton Hospital NHS Trust

• Name: Dr Kim Orchard
• Affiliation: University Southampton Hospital NHS Trust

Key inclusion & exclusion 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 <0.07 µg/L
o NYHA heart failure class of <3
o No more than 3 organs involved by amyloidosis by consensus guidelines.
o Creatinine clearance or isotope GFR =30ml/min.
o Bilirubin =1.5 times and alkaline phosphatase =3 x upper limit of normal.
o AST or ALT <2.5 x upper limit of normal range.
o Mean left ventricular wall thicknesses of <16mm by echocardiography.
o Absence of clinically important amyloid related autonomic neuropathy .
o Absence of clinically important amyloid related gastro intestinal haemorrhage.
• Capable of providing written, informed consent.
• Women of child bearing potential should use adequate forms of contraception.
o Intrauterine Device (IUD)
o Hormonal based contraception (pill, contraceptive injection etc.)
o Double Barrier contraception (condom and occlusive cap e.g. diaphragm or cervical cap with spermicide)
o True abstinence

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

AL-Amyloidosis
MedDRA version: 18.0 Level: LLT Classification code 10024460 Term: Light chain disease myeloma associated System Organ Class: 100000004864

Intervention(s)

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 type: equal

Product Name: Indium­ 111 ­labelled Anti­-CD66
Pharmaceutical Form: Infusion
INN or Proposed INN: Indium 111-radiolabelled anti-CD66
Concentration unit: MBq/kg megabecquerel(s)/kilogram
Concentration type: equal

Product Name: yttrium-90 radiolabelled anti-CD66 antibody
Pharmaceutical Form: Infusion
INN or Proposed INN: Yttrium­90 radiolabelled anti­CD66
Concentration unit: MBq/kg megabecquerel(s)/kilogram
Concentration type: range
Concentration number: 2-5

Primary Outcome(s)

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 Outcome(s)

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

Timepoint(s) of evaluation of this end point: at completion of trial

Secondary ID(s)

RMHCAN1104

Source(s) of Monetary Support

Leukaemia and Lymphoma Research fund

Amyloidosis Research Fund (UCL)