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Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients

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ClinicalTrials.gov Identifier: NCT02994784
Recruitment Status : Recruiting
First Posted : December 16, 2016
Last Update Posted : January 8, 2019
Sponsor:
Collaborator:
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
Shayna Sarosiek, Boston Medical Center

Brief Summary:
This is a single arm, open label study designed to evaluate the safety and efficacy of propylene glycol-free melphalan hydrochloride in patients with AL amyloidosis. Treatment will be comprised of propylene glycol-free melphalan hydrochloride administered intravenously at a dose of 70-100 mg/m2/day on Days -3 and -2 as conditioning prior to autologous stem cell transplantation.

Condition or disease Intervention/treatment Phase
Amyloidosis; Systemic Drug: Propylene Glycol-Free Melphalan Hydrochloride Phase 2

Detailed Description:

This is a single arm, open label study designed to evaluate the safety and efficacy of propylene glycol-free melphalan hydrochloride in patients with AL amyloidosis. Treatment will be comprised of propylene glycol-free melphalan hydrochloride administered intravenously at a dose of 70-100 mg/m2/day on Days -3 and -2 as conditioning prior to autologous stem cell transplantation.

After giving written informed consent, subjects will be evaluated for eligibility for enrollment in the study. Baseline evaluations will be performed as outlined in Section 7. Subjects who satisfy all inclusion and exclusion criteria will begin the study drug. Subjects will be monitored from the time of the medication administration until discharge from the transplant program for safety. Organ function and hematologic status will also be measured at 6 and 12 month follow-up visits.

Standard response criteria for AL amyloidosis hematologic and organ response will be used. Overall response rate will be measured and participants will be categorized into complete response, very good partial response, partial response and progressive disease. Progression free survival, organ response, and safety and tolerability of propylene glycol-free melphalan hydrochloride will be assessed.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Single-Center, Open-Label, Safety and Efficacy Study of Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients Undergoing Autologous Stem Cell Transplantation
Actual Study Start Date : January 8, 2018
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Amyloidosis

Arm Intervention/treatment
Experimental: Evomela
Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation
Drug: Propylene Glycol-Free Melphalan Hydrochloride
Intravenous Propylene Glycol-Free Melphalan Hydrochloride
Other Name: Evomela




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 100 days ]
    To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to renal dysfunction (was acute renal failure is defined as either a >/=1 mg/dL increase in serum creatinine or a doubling of serum creatinine to >/=1.5 mg/dL for at least 2 days.), cardiac dysfunction (new arrhythmia), or autonomic dysfunction (decline in sitting systolic blood pressure of ≥20mm Hg compared to baseline)


Secondary Outcome Measures :
  1. neutrophil engraftment [ Time Frame: 3 weeks ]
    time to neutrophil engraftment

  2. platelet engraftment [ Time Frame: 3 weeks ]
    Assess time to platelet engraftment

  3. treatment related mortality [ Time Frame: 100 days ]
    Number of patients who expire within 100 days of transplant

  4. hematologic overall response rate [ Time Frame: 6 months ]
    Number of patients with response based on Gertz, Palladini criteria

  5. organ response [ Time Frame: 12 months ]
    Number of patients with organ response based on Gertz criteria

  6. number of hospitalizations [ Time Frame: 100 days ]
    Number of hospitalizations per patient



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • Eastern Cooperative Oncology Group Performance Status 0-2
  • Histologic diagnosis of primary systemic (AL) amyloidosis based on:

    • Deposition of amyloid material by Congo red stain showing characteristic apple green birefringence AND
    • Evidence of a clonal plasma cell dyscrasia with monoclonal protein in the serum or urine by immunofixation electrophoresis AND/OR abnormal serum free light chain assay AND/OR clonal plasma cells in the bone marrow exam demonstrated by immunohistochemistry, flow cytometry, or in situ hybridization AND
    • Evidence of organ involvement
  • Eligible for treatment with high dose melphalan and stem cell transplantation per institutional guidelines
  • Ability to understand and willingness to sign informed consent
  • Pulmonary Function Test demonstrating a diffusion capacity of lung for carbon monoxide ≥ 50%
  • Left ventricular ejection fraction ≥40%
  • Systolic blood pressure >90 mm Hg (supine position)
  • Eastern Cooperative Oncology Group Performance status of 2 or better (unless patient is diagnosed with AL amyloidosis involving the gastrointestinal and peripheral/autonomic nervous systems, then performance status of 3 is acceptable)

Exclusion Criteria:

  • Previous high-dose melphalan and stem cell transplant
  • Previous total cumulative dose of oral melphalan > 300 mg
  • Cytotoxic chemotherapy within the previous 28 days
  • New York Heart Association ≥3
  • Decompensated or uncontrolled heart failure
  • Oxygen dependence
  • epidermal growth factor receptor < 30 ml/min
  • Active infection (i.e HIV, Hepatitis B or C)
  • Pregnancy or breastfeeding
  • Exposure to another investigational drug within 3-4 weeks prior to start of study treatment
  • Ongoing alcohol or drug addiction
  • Unable or unwilling to comply with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02994784


Contacts
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Contact: Shayna Sarosiek, MD 617-638-7519 shayna.sarosiek@bmc.org
Contact: Salli Fennessey, BS 617-638-8261 sally.fennessey@bmc.org

Locations
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United States, Massachusetts
Boston Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Contact: Sally Fennessey    617-638-8261    sfenness@bu.edu   
Sponsors and Collaborators
Shayna Sarosiek
Spectrum Pharmaceuticals, Inc
Investigators
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Principal Investigator: Shayna Sarosiek, MD Attending Physician

Publications:
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Responsible Party: Shayna Sarosiek, Sponsor-Investigator, Boston Medical Center
ClinicalTrials.gov Identifier: NCT02994784     History of Changes
Other Study ID Numbers: H-35835
First Posted: December 16, 2016    Key Record Dates
Last Update Posted: January 8, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There are no plans to share individual participant data.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Immunoglobulin Light-chain Amyloidosis
Immunosuppressive Agents
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Paraproteinemias
Melphalan
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunologic Factors
Physiological Effects of Drugs