The purpose of this platform study is to assess the efficacy of different novel treatments/ combinations for patients who have functional high-risk disease, defined as relapsing or refractory within 18 months of first-line myeloma treatment. Patients who have functional high-risk disease currently do not have optimal treatments available via the Pharmaceutical Benefits Scheme and have poorer outcomes compared to myeloma patients who are not considered functional high-risk.

Who is it for?
You may be eligible for this study if you are male or female aged 18 years or older, have a documented diagnosis of multiple myeloma and have relapsed within 18 months following initiation of first-line therapy and require treatment.

Study details
A platform study is designed to make the process of trialing different treatments for the same disease more efficient by making these treatments under one “platform” and therefore under one ethics approval. With the platform, there are different “domains”, analogous to treatment arms. Your treating doctor will decide which domain is potentially suitable for you. Biological samples, such as blood and bone marrow, will be collected to assess how you respond to treatment. These samples will also be used for scientific research to better understand how myeloma changes after using these treatments.

It is hoped that findings from this study will provide information on newer treatments that are not yet available in Australia to treatment functional high-risk myeloma.

Key Inclusion Criteria:

– Age >= 18 years of age.
– Able to provide written consent.
– Documented diagnosis of MM with measurable disease as define by any of the following
– Serum M-component greater than 5 g per L and/or
– Urine M-component greater than200 mg per 24 h, and/or
– Involved serum free light chain level greater than 100mg per L.
– Patients who do not meet these criteria but have biopsy proven extra-medullary disease (extra-osseous plasmacytoma that is not contiguous with an osseous plasmacytoma) that can undergo response evaluation with serial PET-CT are considered to have measurable disease.
– Documented evidence of progressive disease within 18 months of commencing front-line therapy for newly diagnosed MM according to IMWG response criteria
– Patients must have received only 1 prior therapy consisting of an IMID or PI-based induction regimen with or without high dose melphalan conditioned autologous stem cell transplant +/- lenalidomide maintenance.
– No contraindication to the use of any of the study drugs and able to comply with trial requirements.
Adequate liver function (total bilirubin less than 2.0x upper limit of normal (ULN), alanine aminotransferase less than 5.0x ULN) unless considered secondary to MM.
– Absolute neutrophil count greater than or equal to 1.0 x 109 per L. Granulocyte colony-stimulating factor (G-CSF) therapy is permitted on study.
Platelet count greater than or equal to 50 x 109/L (greater than or equal to 30 x 109 per L if MM involvement in the marrow is greater than 50 per cent), patients should not have received platelet transfusions within 7 days of the screening platelet count.
– Hb greater than or equal to 80g per L, red cell transfusions as per institutional protocol are allowed.
– Has provided written informed consent.
– Women of childbearing potential participants must not become pregnant while on study; male participants must not father children while on study

Key Exclusion Criteria:

– Patients who have had myocardial infarction within 6 months prior to enrolment, or New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
– Any other serious or uncontrolled medical or psychiatric illness that could, in the investigators’ opinion, potentially interfere with the completion of treatment according to this protocol.
– Known ongoing or active systemic infection, active hepatitis B or C infection, or known human immunodeficiency virus positivity. Patients with latent TB can proceed on study provided adequate prophylaxis has been commenced.
– Known autoimmune disease requiring ongoing immunosuppression
– Women who are pregnant or lactating. Women of child-bearing potential must have a negative pregnancy test (minimum sensitivity of at least 25 mIU per mL) at Screening.
– Active malignancy with the exception of any of the following:
o Adequately treated basal cell carcinoma, squamous cell carcinoma or in situ cervical cancer.
o Adequately treated stage 1 cancer from which the subject is currently in remission from and has been in remission for greater than 2 years.
o Stage 1 prostate cancer that does not require treatment.
o Any other cancer from which the subject has been disease-free for greater than 2 years.
– Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
– Participation in other clinical trials for the treatment of MM, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial

Louise Hay
louise.hay@health.wa.gov.au
08 6383 3207

Australian Government Department of Health and Aged Care: Medical Research Future Fund

Australasian Myeloma Research Consortium

Phase 2

ZEPFHR-MM