A Evaluation of the Safety of Oncocort IV Pegylated Liposomal Dexamethasone Phosphate in Patients With Progressive Multiple Myeloma (AMETHYST)
Primary Purpose
Multiple Myeloma
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Liposomal Dexamethasone, Targeted Drug Delivery
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
IV Liposomal Dexamethasone
Arm Description
IV Liposomal Dexamethasone given 1 to 4 times in total over period of maximally 4 weeks
Outcomes
Primary Outcome Measures
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Secondary Outcome Measures
Response according to IMWG Criteria
Percentage change of myeloma-related measures
Quality of life questionnaire
Peak Plasma Concentration (Cmax)
Area under the plasma concentration versus time curve (AUC)
Full Information
NCT ID
NCT03033316
First Posted
January 3, 2017
Last Updated
November 4, 2020
Sponsor
Enceladus Pharmaceuticals BV
Collaborators
University Hospital, Aachen, Accelovance
1. Study Identification
Unique Protocol Identification Number
NCT03033316
Brief Title
A Evaluation of the Safety of Oncocort IV Pegylated Liposomal Dexamethasone Phosphate in Patients With Progressive Multiple Myeloma
Acronym
AMETHYST
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Terminated
Why Stopped
Patient enrolment issues
Study Start Date
January 2017 (Actual)
Primary Completion Date
August 2020 (Actual)
Study Completion Date
August 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Enceladus Pharmaceuticals BV
Collaborators
University Hospital, Aachen, Accelovance
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Liposomal Dexamethasone, Targeted Drug Delivery
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IV Liposomal Dexamethasone
Arm Type
Experimental
Arm Description
IV Liposomal Dexamethasone given 1 to 4 times in total over period of maximally 4 weeks
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
Week 8
Secondary Outcome Measure Information:
Title
Response according to IMWG Criteria
Time Frame
4 and 8 weeks after 1st dose
Title
Percentage change of myeloma-related measures
Time Frame
up to 8 weeks after 1st dose
Title
Quality of life questionnaire
Time Frame
up to 8 weeks after 1st dose
Title
Peak Plasma Concentration (Cmax)
Time Frame
during 1st 4 weeks
Title
Area under the plasma concentration versus time curve (AUC)
Time Frame
during 1st 4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
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
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefan Wilop, MD
Organizational Affiliation
RWTH University Clinic Aachen
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Evaluation of the Safety of Oncocort IV Pegylated Liposomal Dexamethasone Phosphate in Patients With Progressive Multiple Myeloma
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