Clinical Trials2022-04-24T14:34:38+00:00

Clinical trials

                                      Welcome to the Amyloidosis Clinical Trials page!

 

This page is designed to be easy to understand for both patients and clinicians alike.

Clinical trials are subdivided into major amyloidosis types: ATTR, AL and Other.

Please SCROLL DOWN for full details.

Clinical trials are listed here once the first health service in Australia has fully opened the trial for patient enrollment.

Once a trial has been listed as being open (or “activated“) at one site, other sites in Australia selected to participate will also be listed, even thought they may not yet be fully open (“pending“).

Please note : Listing a clinical trial on this website does not necessarily equate as endorsement of the trial by the Australian Amyloidosis Network. Any patient interested in a trial should discuss the pros and cons of the studies with their treating practitioner.

For each trial, a description of the trial, including key inclusion and exclusion criteria, and local contacts are provided.

The trial status at each site will be indicated by a symbol.
The key is as follows:

Clinical trial key

Systemic Light Chain Amyloidosis (AL) trials

The “CAEL-101” monoclonal antibody trials for newly diagnosed AL Amyloidosis with cardiac involvement are now open in Australia!

All four AAN services, as well as the Royal Adelaide Hospital, are now recruiting patients to these studies!

CAEL101-301: A Phase 3, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of CAEL-101 and Plasma Cell Dyscrasia Treatment Versus Placebo and Plasma Cell Dyscrasia Treatment in Plasma Cell Dyscrasia Treatment-Naïve Patients with Mayo Stage IIIb AL Amyloidosis

CAEL101-302: A Phase 3, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of CAEL-101 and Plasma Cell Dyscrasia Treatment Versus Placebo and Plasma Cell Dyscrasia Treatment in Plasma Cell Dyscrasia Treatment-Naïve Patients with Mayo Stage IIIa AL Amyloidosis – A Study to Evaluate the Efficacy and Safety of AKCEA-TTR-LRx With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)

What is the drug in question?
CAEL-101 is a monoclonal antibody that attaches itself to part of the AL amyloid fibril in your tissues, and makes it easier for your own immune system to clear the amyloid deposits.

Who is eligible for the trial?
Patients with symptomatic newly diagnosed AL cardiac amyloidosis are eligible for these trials.
Patients who have already had treatment for their AL amyloidosis, or those without significant heart involvement are not eligible/
Does every patient receive the actual trial drug?
These are international Phase 3 prospective randomised placebo-controlled double-blinded studies.
All patients will receive the normal treatment for new diagnosed AL amyloidosis, that being bortezomib (Velcade), cyclophosphamide and dexamethasone.
In addition, patients will be randomized 2:1 to also receive either the CAEL-101 infusion delivered through an IV line into your vein (a “drip”) or the placebo (“dummy” drug) infusion. That means you have a 2 out of 3 chance of receiving the active drug. Neither you nor your doctor will know whether you are on the active drug or the placebo.

How is the drug administered?
CAEL-101 is administered as a intravenous (“a drip into a vein”) infusion. Patients will receive their injection weekly for four weeks then fortnightly.

How long does the trial go for?
At least 50 weeks (almost a year).

Anything else I need to know?
As part of the assessment for the trial, you will need to undergo several 6 minute walking tests, echocardiography (heart ultrasounds), and complete quality of life questionairres.

Key inclusion criteria:
Systemic AL (not ATTR) amyloidosis, involving the heart, as proven by

  1. Biopsy proof for amyloid deposits (such as bone marrow, kidney or heart biopsy)
  2. Cardiac MRI and/or echocardiography demonstrating signs of cardiac amyloidosis
  3. Elevated serum free light chains >40mg/L.
  4. NT-proBNP >650ng/L

Key exclusion criteria:

  1. Patients who have received previous therapy for AL Amyloidosis
  2. Patients whose systolic blood pressure if <90mmHg
  3. Patients on dialysis, or taking high doses of prednisolone or doxycycline.

For more information, please check the five recruiting centres listed below and the Clinical Trials Gov website:

Sites

Queensland

Status:
Site: Queensland Amyloidosis Centre,
Princess Alexandra Hospital, Brisbane
Contact: A/Prof Peter Mollee
Email: amyloidosis@health.qld.gov.au

Victoria

Status:
Site: Victorian and Tasmanian Amyloidosis Centre, Eastern Health, Melbourne
Contact: Simon Gibbs
simon.gibbs@monash.edu

South Australia

Status:
Site: Royal Adelaide Hospital, Adelaide
Contact: Dr Noemi Horvath
Email:TBC

New South Wales

Status:
Site: Westmead Hospital, Sydney
Contact: Dr Fiona Kwok
Email: WSLHD-TTRtrials@health.nsw.gov.au

Western Australia

Status:
Site: Fiona Stanley Hospital, Perth
Contact: Dr Hasib Sidiqi
Email: coral.almeida@health.wa.gov.au
Hasib.Sidiqi@health.wa.gov.au

A Phase Ib/II Open-Label Study of APG2575 in Combination with Novel Therapeutic Regimens in Subjects with Relapsed or Refractory Multiple Myeloma and Immunoglobulin Light Chain Amyloidosis

APG-2575 (varying doses) + pomalidomide and dexamethasone (Pd)

What is the drug in question?
Approximately 50% of patients with AL amyloidosis have a chromosomal (genetic) change involving part of chromosome 11 swapping with part of chromosome 14, referred to as “t(11;14)”. BCL-2 inhibitors target this mutation and can cause cell death of the plasma cells that make the amyloid. APG-2575 is a novel BCL-2 inhibitor.

In this study, APG-2575 is combined with pomalidomide, an immunomodulatory drug which has been used extensively in myeloma, and appears to be effective and well tolerated in AL amyloidosis too. Dexamethasone, a steroid, is also combined with APG-2575 and pomalidomide, to hopefully enhance the effect of the drug.
During the study, patients will be assigned different doses of APG-2575 to determine the highest dose that is the best tolerated.

Who is eligible for the trial?
Any patient with relapsed AL amyloidosis with organ involvement (eg. heart and/or kidneys), or a patient who has not achieved an excellent response to their first 3 cycles of front-line chemotherapy.

Does every patient receive the actual trial drug?
Yes, all patients receive APG-2575, pomalidomide and dexamethasone

How is the drug administered?
This is an all oral, tablet treatment

How long does the trial go for?
Patients will continue to receive treatment until disease progression, unacceptable toxicity, or withdrawal of consent.

Key inclusion criteria:
Systemic AL (not ATTR) amyloidosis, involving the heart, as proven by

  1. ≥ 18 years of age.
  2. Histochemical diagnosis based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens, the type must have been confirmed unequivocally.
  3. Symptomatic organ involvement.
  4. At least one prior line of systemic therapy for AL. Patients who do not achieve at least a PR to frontline therapy in 3 months are eligible.
  5. All MM/AL patients should have measurable disease as defined by at least ONE of the following:
    • Serum monoclonal protein 1.0 g/dl or more by protein electrophoresis.
    • >200 mg of monoclonal protein in the urine on 24-hour electrophoresis.
    • If both serum and urine monoclonal proteins are non-measurable:
    • Serum differential FLC concentration (dFLC) > 5 mg/dL; OR serum FLC of 7.5 mg/dL provided the κ/λ FLC ratio is abnormal
  6. Eastern Cooperative Oncology Group (ECOG) ≤ 2.
  7. Life expectancy ≥ 6 months.
  8. Adequate hematologic function defined as:
    • ANC ≥1.0 x 109/L independent of growth factor support within 7 days of the first dose with study drug.
    • Haemoglobin ≥8 g/dL without transfusion or growth factor support within 7 days of the first dose of study drug.
    • Platelet count ≥ 100 x 109/L or ≥ 50 x 109/L if bone marrow involvement independent of transfusion support
  9. Adequate hepatic and renal function defined as:
    • AST and ALT < 3 x upper limit of normal
    • Creatinine ≤3 mg/dL and CrCL ≥25 ml/min using the Cockcroft-Gault formula
    • Bilirubin< 1.5 x ULN (except if considered secondary to Gilbert’s syndrome and primarily indirect bilirubinemia)
  10. PT/INR ≤2 x ULN and PTT (or aPTT) ≤2 x ULN.
  11. Female subjects who are of non-reproductive potential. Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
  12. Male and female subjects who agree to use highly effective methods of birth control during the period of therapy and for 90 days after the last dose of study drug.
  13. Ability to cooperate to complete neurological examinations if required

Key exclusion criteria:

  1. AL amyloidosis patients who have not been treated with any systemic therapy
  2. AL amyloidosis clinically overt multiple myeloma i.e. original CRAB criteria. Extent of marrow plasmacytosis is not prohibitive.
  3. Subject has received antineoplastic therapy within 2 weeks before the date of initiating study treatment.
  4. Subjects planning to undergo a stem cell transplant prior to progression of disease on this study, i.e., these subjects should not be enrolled in order to reduce disease burden prior to transplant.
  5. Subject has peripheral neuropathy ≥grade 3 except caused by AL amyloidosis.
  6. Active cardiovascular disease, such as uncontrolled arrhythmia (including Frederica corrected QT interval (QTc ≥470 msec) or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction or unstable angina.
  7. Major surgical procedure within ≤14 days prior to initiating study treatment, or anticipation of the need for major surgery during the course of the study treatment, radiotherapy ≤14 days prior to initiating study treatment, systemic treatment within 14 days before the first dose of APG2575.
  8. Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.
  9. Subject has any concurrent or recent malignancy ≤ 1 year prior to registration with the exception of: basal or squamous cell skin cancer, any carcinoma in situ.

ACCESS CLINICAL TRAILS DATABASE HERE

Sites

Victoria

Status:
Site: Epworth Freemasons, Melbourne
Contact: Dr Simon Gibbs
Email: simon.gibbs@monash.edu

A Phase II trial to evaluate the efficacy of Isatuximab plus Pomalidomide and Dexamethasone in patients with AL amyloidosis not in VGPR or better after any previous therapy

What is the drug in question?
Isatuximab is a monoclonal antibody that attacks the amyloid-forming plasma cells and helps your own immune system to kill these abnormal cells. It is very similar to daratumumab which is a highly effective treatment in AL amyloidosis.
Pomalidomide is an immunomodulatory drug which has been used for many years in myeloma, and has been shown to be effective and well tolerated in AL amyloidosis.
Dexamethasone is a steroid which also acts to suppress the production of the amyloid-forming plasma cells, and is usually combined with other treatments to improve their efficiency in destroying the amyloid-causing plasma cells and light chains.

Who is eligible for the trial?
Any patient with AL amyloidosis who have received at least one line of treatment with cyclophosphamide or melphalan and/or Velcade or ixazomib, and dexamethasone and not be in VGPR or better at the time of inclusion.

A “VGPR” stands for “Very Good Partial Response”, which is when the amyloid-making light chain is not more than 40mg/L greater than the other light chain. For instance, a patient with a lambda light chain of 55mg/L and a kappa light chain of 20mg/L would usually be consider in VGPR if the lambda light chains were the amyloid-causing light chains.

Does every patient receive the actual trial drug?
Yes, all patients receive isatuximab, pomalidomide and dexamethasone treatment.

How is the drug administered?
Pomalidomide and dexamethasone are oral tablets, while isatuximab is an intravenous (IV; through a “drip” in your arm) infusion.

Isatuximab will be given weekly for the first month then fortnightly for the remainder of the 12 month trial.

Pomalidomide is a tablet taken every day for 3 weeks then you have a week off. This is repeated every 4 weeks.
Dexamethasone is tablet taken once per week.

How long does the trial go for?
The trial will run for up to 12 months, but for those patients who achieve a complete 100% response to the treatment, the trial finishes after 9 months. However, patients will be followed up after the trial finishes every few months for up to 4 years.

Anything else I need to know?
Patients with myeloma bone disease and/or who have previously received daratumumab are not eligible for this study.

Key inclusion criteria:

  1. Age: ≥18
  2. Histologic diagnosis of AL amyloidosis
  3. Patients should have received at least one line with an alkylating agent and/or a PI, and dexamethasone and not be in VGPR (or better) at the time of inclusion (patients who did not reach VGPR before, or patients in VGPR or better before but with a hematological relapse at the time of inclusion can be included)
  4. Measurable hematologic disease: difference between involved and uninvolved FLC > 50 mg/L with an abnormal k/l ratio
  5. Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system)
  6. Wash-out period of at least 4 weeks from previous antitumor therapy or any investigational treatment or 5 half‐lives from previous antibodies, whichever is longer.
  7. Adequate bone marrow function prior to 1st drug intake (C1D1), without transfusion or growth factor support within 5 days prior to 1st drug intake, defined as:
    – Absolute neutrophils count ≥ 1000/mm3,
    – Platelets ≥ 75000/mm3,
    – Hemoglobin ≥ 8.0 g/dL,
  8. Adequate organ function defined as:
    – Serum ASAT or ALAT ≤ 3.0 X Upper Limit of the Normal range (ULN),
    – Serum total bilirubin level < 1.5 x ULN, unless for subjects with Gilbert’s syndrome where thedirect bilirubin should then be ≤ 2.0 x ULN.
  9. ECOG status ≤ 2
  10. Male participants must agree to use contraception during the intervention period and for at least 5 months after the last dose of IsaPd treatment and refrain from donating sperm during this period.
  11. Female participants are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies:
    – Not a Female of childbearing potential (FCBP), OR
    – a FCBP must have a negative serum or urine pregnancy test and must either commit to continue complete abstinence from heterosexual intercourse or apply two acceptable methods of birth control

Key exclusion criteria:

  1. Presence of non-AL amyloidosis.
  2. AL amyloidosis with isolated soft tissue involvement.
  3. Bone marrow plasma cells > 30% and clinically symptomatic multiple myeloma with lytic bone lesions;
  4. NT-proBNP > 8500 ng/L and hs-troponin I > 100 ng/L or hs-troponin T > 50 ng/L (cardiac stage IIIb patients);
  5. Repetitive ventricular arrhythmias on 24h Holter ECG despite anti‐arrhythmic treatment sustained ventricular tachycardia, aborted ventricular fibrillation, atrioventricular nodal or sinoatrial nodal dysfunction with no pacemaker.
  6. Chronic atrial fibrillation with uncontrolled heart rate.
    Significant cardiac dysfunction; myocardial infarction within 12 months; unstable poorly controlled angina pectoris;
  7. Uncorrected valvular disease unrelated to AL amyloid cardiomyopathy,
    QT interval as corrected by Fridericia’s formula > 550 msec without pacemaker,
    Undergoing dialysis.
  8. Ongoing toxicity (excluding alopecia and those listed in eligibility criteria) from any prior therapy > Grade 1 (NCI-CTCAE v5.0)
  9. Supine systolic blood pressure < 90 mmHg, or symptomatic orthostatic hypotension, defined as a systolic blood pressure upon standing < 80 mmHg despite medical management (i.e. midodrine, fludrocortisones) in the absence of volume depletion.
  10. Previous anti-CD38 therapy or pomalidomide therapy (if refractory to pomalidomide).
  11. Hypersensitivity to IMiD® defined as any hypersensitivity reaction leading to stop IMiD® within the 2 first cycles or toxicity, which does meet intolerance definition
    History of malignancy within 3 years before the date of inclusion (exceptions are squamous and basal cell carcinomas of the skin, carcinoma of the skin, carcinoma in situ of the cervix or breast).
  12. Active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics.
  13. Received any investigational drug within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer. In case of very aggressive disease delay could be shortened after agreement between sponsor and investigator, in absence of residual toxicities from previous therapy.
  14. Known positive for HIV or active hepatitis A, B or C.
  15. Pregnant of breast-feeding females.

ACCESS CLINICAL TRAILS DATABASE HERE

Sites

Victoria

Status:
Site: Eastern Health, Melbourne
Contact: Dr Simon Gibbs
Email: simon.gibbs@monash.edu

Queensland

Status:
Site: Princess Alexandra Hospital, Brisbane
Contact: Associate Professor Peter Mollee
Email: amyloidosis@health.qlg.gov.au

Western Australia

Status:
Site: Fiona Stanley Hospital, Perth
Contact: Associate Professor Hasib Sidiqi
Email: hasib.sidiqi@wa.health.gov.au

South Australia

Status:
Site: Royal Adelaide Hospital
Contact: Dr Noemi Horvath
Email: TBC

Please check this website weekly for updates!

————————————–

Transthyretin Amyloidosis (ATTR) trials

The “Cardio TTRansform” trial for ATTR Amyloidosis is now open in Australia!

Please click on the links below for more details.

If the Cardio TTRansform study isn’t right for you or not available in your area, there are still treatments for ATTR readily available off-trial that your doctor can discuss with you. These include:

  • Diflunisal (similar to tafamidis) – available at all AAN services
  • Doxycycline and/or
  • EGCG (green tea extract).
A Study to Evaluate the Efficacy and Safety of AKCEA-TTR-LRx With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)

What is the drug in question?

AKCEA-TTR-LRx is a gene-silencing therapy, designed to reduce the production of TTR by the liver, and thus slow or stop the formation and progression of TTR amyloidosis.

Who is eligible for the trial?

Patients with symptomatic ATTR cardiac amyloidosis are eligible for this trial.

Both ATTRwt (wild-type) and ATTRv (hereditary) disease groups are included.

Does every patient receive the actual trial drug?

This is an international Phase 3 prospective randomised placebo-controlled double-blinded study.

Patients will be randomized 1:1 (50;50 chance) to receive either the AKCEA-TTR-LRx injection or the placebo (“dummy” drug) injection. Neither you nor your doctor will know whether you are on the active drug or the placebo.

How is the drug administered?

AKCEA-TTR-LRx is administered as a subcutaneous (“under the skin”) injection. Patients will receive their injection every four weeks

How long does the trial go for?

The TTRansform trial lasts 120 weeks (27 months).

Anything else I need to know?

Patients can also take EGCG and/or tafamidis during the study, but not diflunisal or doxycycline.

N.B. Neither EGCG nor Tafamidis will be supplied by the drug company, and tafamidis is currently not available on the PBS.

Key inclusion criteria:

1. “Symptomatic” heart failure defined as requiring hospitalisation or current/prior diuretic management.

2. NT-proBNP 600-6000 ng/L.

Key exclusion criteria:

1. Monoclonal gammopathy of undetermined significance (MGUS) unless fat, bone marrow, or heart biopsy confirms the absence of AL amyloid by mass spectrometry or immunoelectron microscopy.

2. eGFR <30mL/min/1.73 m2

3. Prior liver or heart transplant.

Access Clinical Trials Database

Sites

New South Wales

Status:
Site: Liverpool Hospital, Sydney
Contact: Study co-ordinator: Natalia Inness: natalia.inness@health.nsw.gov.au
Principal Investigator: Gayathri.Kumarasinghe@health.nsw.gov.au
Phone: (02) 8738 3078
Fax: (02) 8738 3054.
Status:
Site: Westmead Hospital, Sydney
Contact: Dr Mark Taylor
Email: WSLHD-TTRtrials@health.nsw.gov.au

Victoria

Status:
Site: The Victorian and Tasmanian Amyloidosis Service, Box Hill Hospital, Melbourne
Email: simon.gibbs@monash.edu
Phone: 03 9094 9505

Tasmania

Status:
Site: Royal Hobart Hospital
Contact: Dr Dave Russell, Cardiologist,
Email: Dave.russell@ths.tas.gov.au

Queensland

Status:
Site: Princess Alexandra Hospital, Brisbane
Contact: Cindy Hall, Study Co-ordinator
Phone: 07 3176 5145

Western Australia

Status:
Site: Genesis Care, Perth
Contact: Dr Peter Purnell
Email: cardiology.research@genesiscare.com