Multiple MyelomaPhase 1/2AMETHYSTNCT03033316
A Evaluation of the Safety of Oncocort IV Pegylated Liposomal Dexamethasone Phosphate in Patients With Progressive Multiple Myeloma
A Phase 1/2 study testing Dexamethasone in people with Multiple Myeloma, run by Enceladus Pharmaceuticals BV.
Trial summary
Oncocort Dexamethasone sodium phosphate encapsulated in so-called 'long-circulating' PEGylated liposomes is in development with the prospect of providing enhanced and prolonged lesion uptake of dexamethasone and therefore increased therapeutic benefit over existing formulations of dexamethasone in Multiple Myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to Aug 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- Previously diagnosed symptomatic MM according to International Myeloma Working Group (IMWG) criteria 1.1. Previously treated with at least two therapy lines including at least one proteasome-inhibitor and at least one immunomodulatory drug 1.2. Relapse after or progressive disease under last therapy according to IMWG criteria.
- At least 18 years old
- Measurable disease (M-protein and/or free light chains) in serum and/or urine
- Willing and able to comply the study protocol visits and assessments
- Willing to use highly effective methods of birth control (see section 7.1.3)
- Written informed consent prior to study participation
Who cannot join
- Types of Multiple Myeloma previously shown to be irresponsive to dexamethasone monotherapy during the last 6 months
- Plasma cell leukemia
- Subject with positive hepatitis panel (including hepatitis B surface antigen [HBsAg], and / or anti-hepatitis B core antibodies, and / or hepatitis C virus antibody [anti-HCV]), and / or a positive HIV antibody screen
- Severe abnormal organ function function or laboratory results at the time of the Screening Visit: WBC <3.0 g/L, ANC <1.5 G/L, PLT <50 G/L, Sodium <135 mmol/L or >150 mmol/L, potassium <3.5 mmol/L or >5.5 mmol/L, calcium <2.0 mmol/L or > 2.9mmol/L, phosphorus <0.8 mmol/L, total bilirubin >1.5x ULN, AP >2.5x ULN, gammaGT >3x ULN, ALT >3x ULN, CK >2.5x ULN, Creatinine >2x ULN, fasting glucose >250 mg/dL, albumin <3 g/dL, cholesterol > 300 mg/dL
- Treatment with oral or injectable (including intra-articular) corticosteroids (CS) within 4 weeks prior to Screening Visit. Inhaled and dermal corticosteroid formulations are allowed
- Subjects who have received a chemotherapeutic treatment cycle including dexamethasone within 4 weeks prior to the Screening Visit
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- Known sensitivity to any component of the study drug or previous hypersensitivity reaction or other clinically significant reaction to intravenous medications, biologic therapy or IV radiocontrast agents
- Active infection requiring systemic treatment
- Planned major surgery during the study period or had undergone major surgery within 30 days prior to the Screening visit
- Pregnancy or breastfeeding
- Any clinically significant hepatic, renal, cardiac, pulmonary, gastrointestinal, metabolic or endocrine disturbances, other medical or psychiatric condition, or clinically relevant abnormal values on any investigation, in the opinion of the Investigator, that could make the subject unsuitable for the study, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study, including severe neuropathies or other painful conditions that might interfere with pain evaluation
- Participation in another clinical investigation less than 4 weeks prior to inclusion
- The subject has a history of any other illness, which, in the opinion of the Investigator, might pose an unacceptable risk by administering study medication.
- The subject has any current or past medical condition and/or required medication to treat a condition that could affect the evaluation of the study
- The subject is unwilling or unable to follow the procedures outlined in the protocol
- The subject is mentally or legally incapacitated
- Persons who are in a relationship of dependence to the Investigator or the Sponsor
About this study
Official title: A Phase I-IIa, Open Label, Multi-Center, Dose Escalating Study to Evaluate the Safety of Intravenous Pegylated Liposomal Dexamethasone Sodium Phosphate (Oncocort) as Monotherapy in Patients With Previously Treated Progressive Multiple Myeloma
Oncocort Dexamethasone sodium phosphate encapsulated in so-called 'long-circulating' PEGylated liposomes is in development with the prospect of providing enhanced and prolonged lesion uptake of dexamethasone and therefore increased therapeutic benefit over existing formulations of dexamethasone in Multiple Myeloma. The current trial is a first-in-man study with Oncocort monotherapy with the objective to assess safety, tolerability, efficacy and dose response after short-term treatment with repeated infusions.
Read the detailed description
This open label multicenter study will evaluate the safety and efficacy of I.V. Oncocort Dexamethasone sodium phosphate given as a short term induction therapy in Multiple Myeloma patients. It consist of a Phase 1 part with a maximum number of 5 ascending dose levels while additional patients will be treated in the Phase 2a part with the recommended phase 2 dose to obtain additional safety data and preliminary efficacy data in multiple myeloma patients. For the dose escalation phase 1 part, 3 patients per dose level will be enrolled. If one patient reaches DLT, another 3 patients will be enrolled in the same dose level. If two or more patients reach DLT in one dose level, maximum tolerated dose (MTD) is defined at the last dose level beneath DLT. Not more than 5 dose level groups are anticipated for this part of the study. MTD will be the Recommended Phase II Dose (RPTD) for the phase IIa part of the study. For the phase 2a part, 7 additional patients will be enrolled at the RPTD dose level, bringing the total number of patients monitored for responses at this dose level to at least 10.
- Conditions
- Multiple Myeloma
- Being tested
- Dexamethasone
- Keywords
- Multiple Myeloma, Liposomal Dexamethasone, Targeted Drug Delivery
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
| Study group | Role | What they receive |
|---|---|---|
| IV Liposomal Dexamethasone | Experimental | IV Liposomal Dexamethasone given 1 to 4 times in total over period of maximally 4 weeks Receives: Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: Week 8
Secondary outcomes (5)
Response according to IMWG Criteria
Measured: 4 and 8 weeks after 1st dose
Percentage change of myeloma-related measures
Measured: up to 8 weeks after 1st dose
Quality of life questionnaire
Measured: up to 8 weeks after 1st dose
Peak Plasma Concentration (Cmax)
Measured: during 1st 4 weeks
Area under the plasma concentration versus time curve (AUC)
Measured: during 1st 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionAug 2020
- Study completionAug 2020
Why it stopped: Patient enrolment issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Enceladus Pharmaceuticals BV
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University Hospital, Aachen, Accelovance
- Responsible party
- Sponsor
- Investigators
- Stefan Wilop, MD, Principal investigator, RWTH University Clinic Aachen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03033316
- Sponsor's protocol ID
- 14-097
- Acronym
- AMETHYST
- Status last verified
- Nov 2020
- First submitted
- 3 Jan 2017
- Last updated
- 6 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-IIa, Open Label, Multi-Center, Dose Escalating Study to Evaluate the Safety of Intravenous Pegylated Liposomal Dexamethasone Sodium Phosphate (Oncocort) as Monotherapy in Patients With Previously Treated Progressive Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03033316
- Acronym / sponsor ID
- AMETHYST / 14-097
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Liposomal Dexamethasone, Targeted Drug Delivery
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Patient enrolment issues
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Enceladus Pharmaceuticals BVIndustry (pharma, biotech, devices)
- Collaborators
- University Hospital, Aachen, Accelovance
- Study start
- Jan 2017 (actual)
- Primary completion
- Aug 2020 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 26 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Oncocort Dexamethasone sodium phosphate encapsulated in so-called 'long-circulating' PEGylated liposomes is in development with the prospect of providing enhanced and prolonged lesion uptake of dexamethasone and therefore increased therapeutic benefit over existing formulations of dexamethasone in Multiple Myeloma. The current trial is a first-in-man study with Oncocort monotherapy with the objective to assess safety, tolerability, efficacy and dose response after short-term treatment with repeated infusions.
Detailed description
This open label multicenter study will evaluate the safety and efficacy of I.V. Oncocort Dexamethasone sodium phosphate given as a short term induction therapy in Multiple Myeloma patients. It consist of a Phase 1 part with a maximum number of 5 ascending dose levels while additional patients will be treated in the Phase 2a part with the recommended phase 2 dose to obtain additional safety data and preliminary efficacy data in multiple myeloma patients. For the dose escalation phase 1 part, 3 patients per dose level will be enrolled. If one patient reaches DLT, another 3 patients will be enrolled in the same dose level. If two or more patients reach DLT in one dose level, maximum tolerated dose (MTD) is defined at the last dose level beneath DLT. Not more than 5 dose level groups are anticipated for this part of the study. MTD will be the Recommended Phase II Dose (RPTD) for the phase IIa part of the study. For the phase 2a part, 7 additional patients will be enrolled at the RPTD dose level, bringing the total number of patients monitored for responses at this dose level to at least 10.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IV Liposomal Dexamethasone | Experimental | Drug: DexamethasoneIV Liposomal Dexamethasone given 1 to 4 times in total over period of maximally 4 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Previously diagnosed symptomatic MM according to International Myeloma Working Group (IMWG) criteria 1.1. Previously treated with at least two therapy lines including at least one proteasome-inhibitor and at least one immunomodulatory drug 1.2. Relapse after or progressive disease under last therapy according to IMWG criteria.
- At least 18 years old
- Measurable disease (M-protein and/or free light chains) in serum and/or urine
- Willing and able to comply the study protocol visits and assessments
- Willing to use highly effective methods of birth control (see section 7.1.3)
Key exclusion criteria (17 listed)
- Types of Multiple Myeloma previously shown to be irresponsive to dexamethasone monotherapy during the last 6 months
- Plasma cell leukemia
- Subject with positive hepatitis panel (including hepatitis B surface antigen [HBsAg], and / or anti-hepatitis B core antibodies, and / or hepatitis C virus antibody [anti-HCV]), and / or a positive HIV antibody screen
- Severe abnormal organ function function or laboratory results at the time of the Screening Visit: WBC <3.0 g/L, ANC <1.5 G/L, PLT <50 G/L, Sodium <135 mmol/L or >150 mmol/L, potassium <3.5 mmol/L or >5.5 mmol/L, calcium <2.0 mmol/L or > 2.9mmol/L, phosphorus <0.8 mmol/L, total bilirubin >1.5x ULN, AP >2.5x ULN, gammaGT >3x ULN, ALT >3x ULN, CK >2.5x ULN, Creatinine >2x ULN, fasting glucose >250 mg/dL, albumin <3 g/dL, cholesterol > 300 mg/dL
- Treatment with oral or injectable (including intra-articular) corticosteroids (CS) within 4 weeks prior to Screening Visit. Inhaled and dermal corticosteroid formulations are allowed
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dexamethasone | Drug | IV Liposomal Dexamethasone |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: Week 8
5 secondary outcomes
Response according to IMWG Criteria
Time frame: 4 and 8 weeks after 1st dose
Percentage change of myeloma-related measures
Time frame: up to 8 weeks after 1st dose
Quality of life questionnaire
Time frame: up to 8 weeks after 1st dose
Peak Plasma Concentration (Cmax)
Time frame: during 1st 4 weeks
Area under the plasma concentration versus time curve (AUC)
Time frame: during 1st 4 weeks
Results and safety
The study was stopped early (reason given: Patient enrolment issues). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan Wilop, MD principal investigator
RWTH University Clinic Aachen
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dexamethasone in people with Multiple Myeloma, run by Enceladus Pharmaceuticals BV.
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 6 inclusion and 17 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 6 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study was stopped early (reason given: Patient enrolment issues). Results are not available in the source record.
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 treatment-related adverse events as assessed by CTCAE v4.0 (time frame: Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Nov 2020.