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

Newly diagnosed:

AFFIRM-AL (NEOD001-301): A Phase 3 Randomized, MultI-Centre Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Birtamimab Plus Standard of Care vs Placebo Plus Standard of Care in Newly Diagnosed Mayo Stage IV Subjects with Light Chain AL Amyloidosis

What is the drug in question?
Birtamimab – this is a monoclonal antibody that attaches to the amyloid deposits and hopefully this promotes your own immune system to clear the amyloid deposits in your body. This is combined with the typical standard treatment, usually “VCD” chemotherapy.

Who is eligible for the trial?
Newly diagnosed patients with systemic AL amyloidosis with advanced disease in the heart.

Does every patient receive the actual trial drug?
Two out of every three patients will receive birtamimab and one out of three will receive a placebo (“dummy”) drug. Neither you nor your treating team will know which drug you are on.

How is the drug administered?
Birtamimab is given through an IV (drip into the vein) every 28 days

How long does the trial go for?
Once 135 patients have received at least 9 months of treatment, the data will be analysed, and a decision of whether to stop the trial or continue will be made then.

Anything else I need to know?
This trial has been previously performed in patients with newly diagnosed AL amyloidosis but only those with advanced heart disease appeared to possibly benefit. This current trial called “AFFIRM” is looking to see whether a benefit can be proven in more advanced heart disease when a larger number of patients are analysed.rres.

Key inclusion criteria:

  1. Newly diagnosed, treatment naive systemic AL amyloidosis with:
    1. Bone marrow demonstrating clonal plasma cells
    2. Confirmed diagnosis of AL amyloidosis by the following:
      1. Histochemical diagnosis of amyloidosis determined by polarizing light microscopy of green birefringent material in Congo red-stained tissue specimens OR characteristic electron microscopy appearance AND
      2. Confirmatory immunohistochemistry OR mass spectroscopy of AL amyloidosis
  2. Cardiac involvement as defined by all of the following:
    • Past documented or presently noted clinical signs and symptoms supportive of a diagnosis of heart failure due to amyloidosis in the absence of an alternative explanation for heart failure
    • Either an endomyocardial biopsy demonstrating AL amyloidosis OR an echocardiogram demonstrating a mean left ventricular wall thickness at diastole >12 mm in the absence of other causes (e.g., severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening
  3. Confirmed Mayo Stage IV as defined by:
    • NT-proBNP ≥1800 pg/mL and
    • Troponin-T >0.03 ng/mL and
    • dFLC ≥18 mg/dL
  4. Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly
  5. Adequate bone marrow reserve, hepatic function, and renal function, as demonstrated by:
    • Absolute neutrophil count ≥1.0 × 109/L
    • Platelet count ≥75 × 109/L
    • Hemoglobin ≥9 g/dL
    • Total bilirubin ≤ 2 × the upper limit of normal (ULN)
    • Aspartate aminotransferase (AST)≤3 × ULN
    • Alanine aminotransferase (ALT) ≤3 × ULN
    • Alkaline phosphatase (ALP) ≤5 × ULN
    • Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2
  6. Seated systolic blood pressure (BP) 90 to 180 mmHg
  7. Distance walked during Screening 6MWT is >30 meters and <550 meters

Key exclusion criteria:

Subjects must meet none of the following criteria:

  1. Non-AL amyloidosis
  2. NT-proBNP >8500 pg/mL
  3. Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma (Appendix 3)
    *Note that subjects who meet the IMWG definition of symptomatic multiple myeloma with signs and/or symptoms attributable only to associated amyloidosis are potentially eligible upon approval of the Sponsor.
  4. Subject is eligible for and plans to undergo ASCT or organ transplant during the study
  5. Symptomatic orthostatic hypotension that in the medical judgment of the Investigator would interfere with the subject’s ability to safely receive treatment or complete study assessments
  6. Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1- Day 1 Visit
  7. Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease
  8. ECG evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:
    • First degree A V-block
    • Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)
    • Right or left bundle branch block
    • Atrial fibrillation with a controlled ventricular rate (uncontrolled [>110 bpm] ventricular rate is not allowed [determined by an average of 3 beats in Lead II or 3 representative beats if Lead II is not representative of the overall ECG])
  9. Peripheral neuropathy assessed as National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 2 with pain, Grade 3, or Grade 4
  10. Subject is receiving oral or intravenous antibiotics, antifungals, or antivirals within 1 week of Month 1-Day 1 with the exception of prophylactic oral agents
  11. Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1
  12. Prior radiotherapy within 4 weeks of Month 1-Day 1
  13. Major surgery within 4 weeks of Month 1-Day 1 or planned major surgery during the study
  14. Active malignancy with the exception of any of the following:
    • Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
    • Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for 2 years
    • Low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10 ng/mL
    • Any other cancer from which the subject has been disease-free for ≥2 years
  15. History of severe allergy to any of the components of birtamimab such as histidine/L histidine hydrochloride monohydrate, trehalose dehydrate, or polysorbate 20 or history of Grade ≥3 infusion-related AEs or hypersensitivity to another monoclonal antibody, or known hypersensitivity to diphenhydramine (or an equivalent H1 antihistamine) or acetaminophen (or its equivalent, paracetamol)
  16. Prior treatment with plasma cell-directed chemotherapy, birtamimab, daratumumab, 11-1F4, anti-serum amyloid P antibody, doxycycline for amyloid, or other investigational treatment directed at amyloid
  17. History of epilepsy or seizure disorder with the exception of childhood febrile seizures
  18. Waldenström’s macroglobulinemia and/or immunoglobulin M monoclonal gammopathy

For more information, please contact one of the five recruiting centres in
Australia, or use this link.

Sites

New South Wales

Status:
Site: St George Hospital, Sydney
Contact: Principal Investigator: Dr. Shir-Jing Ho
Study Co-ordinator: Lindy Williams
lindy.williams@health.nsw.gov.au
ph: 02 9113 4831

Victoria

Status:
Site: Eastern Health, Melbourne
Contact: Principal Investigator: Dr. Olga Motorna
Study Co-ordinator: Liz Arnold
liz.arnold@monash.edu
ph: 03 9094 9503

Queensland

Status:
Site: ICON Cancer Center South Brisbane
Contact: Principal Investigator: Prof. Kerry Taylor
Study Co-ordinator: Tara Thompson
tara.thompson@icon.team
Ph: 07 3737 4501

Western Australia

Status:
Site: Royal Perth Hospital
Contact: Principal Investigator: Prof. Michael Leahy
Study Co-ordinator: Monika Stoeska
Monika.Stoeska@health.wa.gov.au
Ph: 08 9224 1533

South Australia

Status:
Site: Royal Adelaide Hospital
Contact: Principal Investigator: Dr. Noemi Horvath
Study Co-ordinator: Rino Amato
rino.amato@sa.gov.au
Ph: 08 7074 5719

Relapsed/refractory:

A Phase Ib/II study of Venetoclax, IBERdomide and dexamethasone for patients in first or
second relapse of Multiple myeloma and/or systemic AL amyloidosis with t(11;14)

What is the drug in question?
Iberdomide is a “CelMod”, which is similar to lenalidomide and pomalidomide. It is well tolerated with proven activity in myeloma.
It is hoped that iberdomide to be more effective and less toxic than lenalidomide in the treatment of AL amyloidosis.
Venetoclax, a BCL2 inhibitor, which used in many haematological conditions, but in myeloma and AL amyloidosis, venetoclax specifically targets the effects of t(11;14) mutation.

Who is eligible for the trial?

  • Patients with AL amyloidosis who have relapsed after 1 or 2 lines of treatment previously.
  • Patients must have have the t(11;14) translocation (genetic variation) detected on their bone marrow biopsy (seen in ~50% of all AL amyloidosis patients).
  • Patients must have serum free light chains (SFLC) >100mg/L to qualify

How is the drug administered?
This clinical trial is designed to see if the combination of both medications with the steroid, dexamethasone, has very high response rate, has quicker response times and is well tolerated.
This is an Australian only study of 50 patients.
Note that this treatment is an all oral (tablet) treatment.
You will be given medication to minimise the risk of these side-effects.

How long does the trial go for?
The three medications will continue until it stops working or if the patient has significant sideeffects and/or wants to withdraw from the study.
While this combination is expected to be well tolerated, the more common potential sideeffects of this treatment are low blood counts, rash,  infections and clots.

Sites

Victoria

Status:
Site: Box Hill Hospital, Melbourne.
Contact: Olga Motorna and Stephen Ting
Email: olga.motorna@easternhealth.org.au
Status:
Site: St Vincent’s Hospital, Melbourne.
Contact: Shirlene Sim and Hang Quach
Email: shirlene.sim@svha.org.au

Queensland

Status:
Site: Townsville University Hospital
Contact: Hock Choong Lai
Email: hock.lai@health.qld.gov.au

New South Wales

Status:
Site: Gosford Hospital
Contact: Cecily Forsyth
Email: cecily.forsyth@healthmail.com.au
Status:
Site: Royal North Shore, Sydney
Contact: Ian Kerridge
Email: ian.kerridge@health.nsw.gov.au
Status:
Site: Liverpool Hospital
Contact: Adam Bryant
Email: adam.bryant1@health.nsw.gov.au

South Australia

Status:
Site: Royal Adelaide Hospital
Contact: Angie Yong
Email: Angie.Yong@sa.gov.au
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: Olga Motorna and Stephen Ting
Email: olga.motorna@easternhealth.org.au

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 Angie Yong
Email: Angie.Yong@sa.gov.au
A Single-Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis

What is the drug in question?
This is a novel BCL-2 inhibitor, similar to venetoclax.

Inhibiting BCL-2 can lead to death in tumour cells dependent on BCL-2 activity, including multiple myeloma cells. Venetoclax has activity in relapsed and refractory AL amyloidosis.

This trial hopes to prove that ZN-d5 will be at least as effective as venetoclax in killing amyloid-forming plasma cells.

Who is eligible for the trial?
Patients with relapsed and refractory AL amyloidosis who have had disease relapse/progression or lack of response to 1 to 3 prior lines of therapy.

Does every patient receive the actual trial drug?
All patients will receive active drug. There is no placebo-arm to this study. ZN-d5 is not given with any other therapy.

How is the drug administered?
ZN-d5 is a oral tablet.

How long does the trial go for?
Up to 135 patients will be included in the trial. Subjects will remain on treatment until disease progression, adverse events, withdrawal of consent, death, or the end of the study.

Key inclusion criteria:

  1. A biopsy-confirmed diagnosis of AL amyloidosis based on one of the following: histopathology (positive Congo red-stained tissue confirmed by immunohistochemistry demonstrating light chain deposition without the presence of transthyretin), the presence of characteristic appearance on electron microscopy, or mass spectrometry typing of amyloid.
  2. At least 1, and no more than 3, prior lines of therapy
  3. Measurable disease defined by dFLC ≥ 20 mg/L.
  4. History of organ involvement that included at least one of the following:
    • Renal: albuminuria or non-Bence Jones proteinuria > 0.5 g/day by 24-hour urine collection.
    • Cardiac: mean left ventricular wall thickness on echocardiogram more than 12 mm in the absence of a history of hypertension or valvular heart disease or unexplained low voltage (< 0.5 mV) on ECG; or NT-ProBNP > 332 ng/L (or BNP > 81-ng/L) in the absence of renal failure.
    • Hepatic: hepatomegaly on PE or ultrasound or alkaline phosphatase > 1.5 × the upper limit of normal (ULN).
    • Gastrointestinal: direct biopsy verification of amyloid deposition and gastrointestinal symptoms, such as gastrointestinal bleeding or diarrhea.
    • Neurologic: symmetrical lower extremity sensorimotor peripheral neuropathy or autonomic neuropathy, including gastric motility disorder, pseudo-obstruction, or voiding dysfunction unrelated to direct organ infiltration. Assessment of t(11;14) status by FISH on bone marrow sample.
  5. Adequate time since prior therapy before initiation of treatment with ZN-d5 (at least 3 months from HSCT or the shorter of 60 days or 5 half-lives from previous drug or biologic therapy or any investigational treatment).
  6. ECOG score of ≤ 2.
  7. Adequate bone marrow function as follows:
    • Hemoglobin ≥ 80g/L, neutrophils ≥ 1.5 ×109/L, Platelets ≥ 50 × 109/L.
  8. Adequate organ function as follows:
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
    • Alkaline phosphatase ≤ 5 × ULN.
    • Total bilirubin ≤ 1.5 × ULN except for subjects with Gilbert syndrome.
    • Serum albumin ≥ 2 g/dL (20 g/L).
    • eGFR ≥ 30 mL/min/1.73 m2

Key exclusion criteria:

  1. Diagnosis of multiple myeloma according to the 2014 International Myeloma Working Group diagnostic criteria.
  2. Mayo 2012 Stage IV disease, defined as follows:
    • NT-ProBNP ≥ 1800 ng/L, cTnT ≥ 0.025 ng/mL, dFLC ≥ 180 mg/L
  3. Any of the following cardiac conditions:
    • New York Heart Association (NYHA) Class III or IV heart failure
    • History of sustained ventricular tachycardia or fibrillation, or ventricular arrhythmias
    • Corrected QT interval (QTc) > 500 msec
    • Second or third-degree atrioventricular block (Mobitz type I is permitted)
    • History of myocardial infarction, coronary stent placement, or coronary artery bypass grafting within 6 months of enrolment
    • Left ventricular ejection fraction (LVEF) by echocardiogram < 35%
    • Supine systolic blood pressure < 90 mm Hg or symptomatic orthostatic hypotension
  4. Positive serum antibody tests for hepatitis B surface antigen or hepatitis C
  5. Concurrent treatment with agents used to treat plasma cell disorders or AL amyloidosis, including experimental agents; such treatments should be discontinued the shorter of 60 days or 5 half-lives prior to first dose of ZN-d5
  6. Prior treatment with ZN-d5, venetoclax, navitoclax, obatoclax or any other small molecule BCL-2 inhibitor
  7. Any concurrent medical condition that would make a potential subject a poor candidate for this study, including uncontrolled serious infection, active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix, uncontrolled pulmonary disease, severe diarrhea, cirrhosis, any condition likely to require systemic corticosteroids for more than 1 week during the course of this study, or major surgery within 28 days of enrolment.

For more information, please contact one of the five recruiting centres in Australia, or please review this site.

Sites

New South Wales

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

Queensland

Status:
Site: Princess Alexandra Hospital
Contact: Dr Emad Abro
Email: amyloidosis@health.qld.org.au

Western Australia

Status:
Site: Sir Charles Gardiner Hospital
Contact: Brad Augustson
Email: Bradley.Augustson@health.wa.gov.au

South Australia

Status:
Site: Royal Adelaide Hospital
Contact: Dr Noemi Horvath and Dr Angie Yong
Email: CALHN.Amyloidtrials@sa.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 Brendan Wisniowski
Ph: 03 8560 4010

Please check this website weekly for updates!

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Transthyretin Amyloidosis (ATTR) trials

Please click on the links below for more details.

Remember that there are non-trial treatments for ATTR readily available that your doctor can discuss with you. These include:

  • Diflunisal – available at all AAN services
  • Doxycycline 
  • EGCG (green tea extract)
  • Tafamidis (via Pfizer access scheme)
Phase I Study of AT-02 in Healthy Volunteers and Subjects With Systemic Amyloidosis (AT02-001)

What is the drug in question?

“AT-02is a full-length, humanised, recombinant immunoglobulin 1(IgG1)-like glycoprotein monoclonal antibody (mAb) fusion protein that has been developed to treat any form of systemic amyloidosis.

Monoclonal antibodies has been used extensively in many disease, including in AL amyloidosis. Drugs such as Daratumumab, rituximab, isatuximab and elotuzumab are all mAbs.

AT-02 has binding potency to ATTR and AL amyloid, and is thought to opsonise amyloid extracts promoting macrophage-mediated phagocytosis of the amyloid.  In other words, the drug “latches onto” amyloid deposits and sends a signal to the immune system to clear deposits from the organ.

Cardiac, renal and hepatic amyloid deposits were shown to regress in mouse studies of this drug.

The most effective and highest well-tolerated dose of AT-02 in amyloidosis patients has not been determined. This Phase I trial is looking at different doses of AT-02  to see how well this drug is tolerated at a single once-off dose, and to determine the “MTD” or maximum tolerated dose.

Who is eligible for the trial?

Patients with ATTR amyloidosis with reasonable renal function (eGFR >30ml/min) are eligible

Does every patient receive the actual trial drug?

All patients will receive active drug. There is no placebo-arm to this study.

How is the drug administered?

AT-02 is an IV infusion through a drip. All patients receive paracetamol, and antihistamine and a steroid to reduce the chance of an infusion-related reaction, such as muscle aches, fevers and shakes, which are often seen during the first infusion of any mAb.

How long does the trial go for?

It is estimated that 30-40 slots will be available for patients in Australia

Patients undergo a cardiac MRI then receive a weekly IV dose of AT02 for 4 weeks

After this, they have a repeat cardiac MRI to see if the amount of amyloid in the heart has decreased.

Then 2 months later, patients will be invited to enrol in the open label extension part of the trial where patients receive a monthly maintenance IV dose to hopefully continue to remove amyloid from the heart

Key inclusion criteria:

  1. Biopsy-proven ATTR amyloidosis or ATTR amyloidosis proven on bone scintigraphy, provided there is no detected plasma cell dyscrasia
  2. Proven cardiac disease: Echocardiogram (heart ultrasound) shows wall thickness inside the heart of >11mm with elevated cardiac biomarkers (blood tests) of NT proBNP and troponin T
  3. Good function state (ECOG score <3) and other organ function

For more information, please contact one of the two recruiting centres in Australia, or please review :

ClinicalTrials.gov Identified: NCT05521022

Sites

Victoria

Status:
Site: Eastern Health, Melbourne
Contact: Name: Olga Motorna
Email: olga.motorna@easternhealth.org.au

Queensland

Status:
Site: Princess Alexandra Hospital
Contact: Name: Dr Dariusz Korczyk
Email: amyloidosis@health.qld.org.au

South Australia

Status:
Site: Flinders Medical Centre
Contact: Name: Fiona Wollaston
Ph: 0422 512 439

Western Australia

Status:
Site: Royal Perth Hospital
Contact: Name: Principal Investigator: Prof Graham Hillis
Study Co-ordinator: Lorraine Hillis
Email: Graham.Hillis@health.wa.gov.au
lorraine.hillis@health.wa.gov.au