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Melflufen and Dexamethasone for Patients with AL Amyloidosis

  • Research type

    Research Study

  • Full title

    An Open-Label, Phase 1/2 Study of Melflufen and Dexamethasone for Patients with AL Amyloidosis

  • IRAS ID

    266757

  • Contact name

    Ashutosh Wechalekar

  • Contact email

    a.wechaleakar@ucl.ac.uk

  • Sponsor organisation

    Oncopeptides AB

  • Eudract number

    2018-002761-19

  • Clinicaltrials.gov Identifier

    116362, IND number

  • Duration of Study in the UK

    3 years, 1 months, 23 days

  • Research summary

    Research Summary
    This is a study of Melflufen and Dexamethasone for patients with plasma cell dyscrasia in immunoglobulin light chain (AL) amyloidosis (rare, progressive disease). Melflufen is an investigational medication, not approved for use in any disease. It has been tested in patients with multiple myeloma (MM) with beneficial effects in some patients. AL amyloidosis and MM are both diseases of the plasma cells (cells that make antibodies or proteins to help fight infection). Melflufen has similarities to a drug called Melphalan which has been used for treatment of AL amyloidosis very effectively.

    Plasma cells are a part of the immune system (the body’s natural ability to fight disease) that make antibodies (proteins that help fight infection). Plasma cells can become abnormal and cause diseases like AL amyloidosis (producing toxic light chain proteins). The plasma cell abnormalities in AL amyloidosis are similar to that in MM. Thus, therapies effective in treating MM are typically used to also treat AL amyloidosis. This research study will evaluate the ability of melflufen to treat AL amyloidosis and the associated side effects of treatment.

    Melflufen will be administered alongside Dexamethasone (a steroid which acts on the immune system) which is used in the treatment of AL amyloidosis. Dexamethasone is often given together with other medications for treating AL amyloidosis and may make medications work better.

    The study is planned to involve up to approximately 46 participants, male and female, aged 18 or over. The study is carried out in cycles. Each cycle is 28 days long and participants may receive up to 8 cycles over 8 months, followed by an end of treatment visit, and then contacted every 3 months for up to 2 years for disease progression follow-up. Procedures include blood, urine, stool and bone marrow sample collection, radiographic assessments, heart assessments and physical examinations.

    Summary of Results
    Study OP201 was a Phase 1/2 study with the objective of exploring the safety and tolerability of melflufen in patients with AL amyloidosis following at least one prior line of therapy. The study was prematurely terminated on 04 November 2021. The Sponsor’s review of the 6 enrolled patients treated with a combination of melflufen (20 mg or 30 mg) and dexamethasone did not reveal any DLTs or SAEs. All AEs observed were Grade 1 or 2. There were no treatment-related dose modifications or dose delays. One patient died during long-term FU. Due to the premature termination and limited data yield as a result, no conclusions could be drawn from this study.

  • REC name

    London - Hampstead Research Ethics Committee

  • REC reference

    19/LO/1568

  • Date of REC Opinion

    2 Dec 2019

  • REC opinion

    Further Information Favourable Opinion