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Amyloidosis; SystemicPhase 2NCT02994784

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

A Phase 2 study testing Propylene Glycol-Free Melphalan Hydrochloride in people with Amyloidosis; Systemic, run by Boston Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Amyloidosis; Systemic
What is being tested?
Propylene Glycol-Free Melphalan Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
8 Jan 2018to 1 Jul 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Boston Medical Center

    Boston, Massachusetts, 02118

Other trials in United States

About this study

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

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.

Read the detailed description

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.

Being tested
Propylene Glycol-Free Melphalan Hydrochloride
Medical subject headings
Immunoglobulin Light-chain Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Propylene Glycol-Free Melphalan HydrochlorideDrug

    Also called Evomela

    Intravenous Propylene Glycol-Free Melphalan Hydrochloride

Study groups in NCT02994784
Study groupRoleWhat they receive
EvomelaExperimentalPropylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation
Receives: Drug: Propylene Glycol-Free Melphalan Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Renal Dysfunction

    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.).

    Measured: 100 days

  2. Number of Participants With Cardiac Dysfunction (New Arrhythmia)

    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 cardiac dysfunction (new arrhythmia).

    Measured: 100 days

Secondary outcomes (6)

  1. Neutrophil Engraftment

    time to neutrophil engraftment

    Measured: 3 weeks

  2. Platelet Engraftment

    Assess time to platelet engraftment

    Measured: 100 days

  3. Treatment Related Mortality

    Number of patients who expire within 100 days of transplant

    Measured: 100 days

  4. Hematologic Overall Response Rate

    Number of patients with response based on Gertz, Palladini criteria (below) Complete response (CR): Normal serum free light chain ratio,Negative serum and urine immunofixation electrophoresis Very good partial response (VGPR): Difference in serum free light chains less than 40 mg/L Partial Response (PR): >50% Reduction in the difference in serum free light chains Stable Disease (SD): Meets neither criteria for CR, VGPR, PR or PD

    Measured: 6 months

  5. Organ Response

    Number of patients with organ response based on Gertz criteria (below)

    • Kidney: 50% reduction in 24-hour urine protein excretion in the absence of progressive renal insufficiency (defined as a 25% increase in serum creatinine, as long as that is > to an absolute increase of 0.5 mg/dL). In the case of nephrotic syndrome: a decrease in proteinuria to < 1g/24h and an improvement in one of 2 extrarenal features - normalization of serum albumin or resolution of edema and/or discontinuation of diuretics in response to improvement in edema.
    • Heart: ≥ 2 mm reduction in the interventricular septal (IVS) thickness by echocardiogram, improvement of ejection fraction by ≥ 20% (echocardiogram must be performed at the same institution), or decrease in 2 NYHA classes without increase in diuretic need.

    Measured: 12 months

  6. Participants With Peri-transplant Hospitalizations

    Number of participants with peri-transplant hospitalizations

    Measured: 100 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2016 (estimated)
  2. Study start8 Jan 2018
  3. Primary completion1 Jul 2022
  4. Study completion1 Jul 2022

Why it stopped: Slow Accrual during COVID pandemic, alternative treatments available. Study halted early.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02994784
Sponsor's protocol ID
H-35835
Status last verified
May 2023
First submitted
18 Nov 2016
Last updated
24 May 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: There are no plans to share individual participant data.

Publications

  • Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, Schonland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A, Klersy C, Merlini G. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012 Dec 20;30(36):4541-9. doi: 10.1200/JCO.2011.37.7614. Epub 2012 Oct 22.

    PubMed 23091105

  • Sarosiek S, Lee MH, Doros G, Edwards CV, Quillen K, Brauneis D, Shelton AC, Sanchorawala V, Sloan JM. Safety and Efficacy of Propylene Glycol-Free Melphalan in Patients with AL Amyloidosis Undergoing Autologous Stem Cell Transplantation: Results of a Phase II Study. Transplant Cell Ther. 2023 Nov;29(11):695.e1-695.e7. doi: 10.1016/j.jtct.2023.08.018. Epub 2023 Aug 20.

    PubMed 37607644

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Propylene Glycol-Free Melphalan Hydrochloride in people with Amyloidosis; Systemic, run by Boston Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Renal Dysfunction (time frame: 100 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02994784, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2023.

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