Back to resultsMEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma (MEDI2228)
Primary Purpose
Relapsed/Refractory Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Dose Escalation, MEDI2228, ADC (antibody drug conjugate)
Dose Expansion, MEDI2228, ADC (antibody drug conjugate)
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed/Refractory Multiple Myeloma focused on measuring multiple myeloma, relapsed/refractory, open-label
Eligibility Criteria
Inclusion Criteria:
- Subjects must be ≥ 18 years of age at the time of screening.
Subjects must have a confirmed diagnosis of relapsed/refractory MM as per IMWG criteria (Rajkumar et al, 2014) and have exhausted standard of care regimens with proven clinical benefit, which include agents from the following anti myeloma therapies: PIs, IMIDs, and mAbs and have measurable disease with at least one of the following criteria:
- Serum M-protein ≥ 0.5 g/dL
- Urine M-protein ≥ 200 mg/24 hours
- Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal.
- Subjects must either be ineligible for or post-autologous stem cell transplant.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Adequate organ and marrow functions as determined per protocol-defined criteria.
Exclusion Criteria
Any of the following would exclude the subject from participation in the study:
Target Disease:
- Subjects who have previously received an autologous stem cell transplant if less than 90 days have elapsed from the time of transplant or the subject has not recovered from transplant associated toxicities prior to the first scheduled dose of MEDI2228
- Subjects who have previously received an allogeneic stem cell transplant
- Central nervous system (CNS) involvement(including meningeal involvement) by MRI or cerebrospinal fluid exam
Known history of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome, plasma cell leukemia, Waldenstrom's macroglobulinemia, or amyloidosis
Medical History and Concurrent Diseases:
- Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose Escalation, MEDI2228, ADC
Dose Expansion, MEDI2228, ADC
Arm Description
Single agent MEDI2228, ADC (antibody drug conjugate) will be administered to adult subjects with relapsed/refractory (R/R) multiple myeloma (MM).
Single agent MEDI2228, ADC (antibody drug conjugate) will be administered to adult subjects with R/R MM in the dose-expansion cohort at the dose selected for evaluation in the dose-expansion phase.
Outcomes
Primary Outcome Measures
Occurrence of adverse events (AEs)
To assess by the occurrence of adverse events (AEs)
Occurrence of SAE (serious adverse events)
To assess the occurrence of serious adverse events (SAEs)
Occurrence of DLTs (dose limiting toxicities)
To assess by the occurrence of hematologic and non-hematologic toxicities, AEs, and abnormal laboratory results
Number of patients with changes in laboratory parameters from baseline
To assess serum chemistry, hematology, coagulation and urninalysis
Number of patients with changes in vital signs from baseline
To assess body temperature, blood pressure and heart rate
Number of patients with changes in elctrocardiogram (ECG) results from baseline
To assess using 12 lead ECG recordings
Secondary Outcome Measures
MEDI2228 maximum observed concentration for PK
To assess the pharmacokinetics of MEDI2228
MEDI2228 area under the concentration-time curve for PK
To assess the pharmacokinetics of MEDI2228
MEDI2228 clearance for PK
To assess the pharmacokinetics of Medi2228
MEDI2228 terminal half-life for PK
To assess the pharmacokinetics of MEDI2228
Number of subjects who develop anti-drug antibodies (ADAs)
To assess immunogenicity of MEDI2228
Objective response rate (ORR)
To assess the anti-tumor activity of MEDI2228
Clinical benefit rate
To assess clinical benefit of MEDI2228
Duration of response (DoR)
To assess the anti-tumor activity of MEDI2228
Progression free survival (PFS)
To assess the anti-tumor activity of MEDI2228
Overall Survival (OS)
To assess the anti-tumor activity of MEDI2228
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03489525
Brief Title
MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma
Acronym
MEDI2228
Official Title
A Phase 1, Open-label Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
May 8, 2018 (Actual)
Primary Completion Date
March 21, 2022 (Actual)
Study Completion Date
March 21, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess the safety, pharmacokinetics and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI2228 in adult subjects with multiple myeloma who are either transplant ineligible or post autologous stem cell transplant and are relapsed/refractory.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Multiple Myeloma
Keywords
multiple myeloma, relapsed/refractory, open-label
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Masking Description
Open-label
Allocation
Non-Randomized
Enrollment
107 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation, MEDI2228, ADC
Arm Type
Experimental
Arm Description
Single agent MEDI2228, ADC (antibody drug conjugate) will be administered to adult subjects with relapsed/refractory (R/R) multiple myeloma (MM).
Arm Title
Dose Expansion, MEDI2228, ADC
Arm Type
Experimental
Arm Description
Single agent MEDI2228, ADC (antibody drug conjugate) will be administered to adult subjects with R/R MM in the dose-expansion cohort at the dose selected for evaluation in the dose-expansion phase.
Intervention Type
Biological
Intervention Name(s)
Dose Escalation, MEDI2228, ADC (antibody drug conjugate)
Intervention Description
Single agent MEDI2228 will be administered to adult subjects with R/R MM. The study aims to evaluate up to 9 planned, sequentially ascending main dose levels
Intervention Type
Biological
Intervention Name(s)
Dose Expansion, MEDI2228, ADC (antibody drug conjugate)
Intervention Description
Adult subjects with R/R MM with measurable disease will be enrolled in the dose-expansion cohort at the dose selected for evaluation in the dose-expansion phase.
Primary Outcome Measure Information:
Title
Occurrence of adverse events (AEs)
Description
To assess by the occurrence of adverse events (AEs)
Time Frame
From time of informed consent through 90 days post end of treatment
Title
Occurrence of SAE (serious adverse events)
Description
To assess the occurrence of serious adverse events (SAEs)
Time Frame
From time of informed consent through 90 days post end of treatment
Title
Occurrence of DLTs (dose limiting toxicities)
Description
To assess by the occurrence of hematologic and non-hematologic toxicities, AEs, and abnormal laboratory results
Time Frame
From time of informed consent through 90 days post end of treatment
Title
Number of patients with changes in laboratory parameters from baseline
Description
To assess serum chemistry, hematology, coagulation and urninalysis
Time Frame
From time of informed consent and up to 21 days post end of treatment
Title
Number of patients with changes in vital signs from baseline
Description
To assess body temperature, blood pressure and heart rate
Time Frame
From time of informed consent and up to 21 days post end of treatment
Title
Number of patients with changes in elctrocardiogram (ECG) results from baseline
Description
To assess using 12 lead ECG recordings
Time Frame
From time of informed consent and up to 21 days post end of treatment
Secondary Outcome Measure Information:
Title
MEDI2228 maximum observed concentration for PK
Description
To assess the pharmacokinetics of MEDI2228
Time Frame
From time of informed consent through 60 days post end of treatment
Title
MEDI2228 area under the concentration-time curve for PK
Description
To assess the pharmacokinetics of MEDI2228
Time Frame
From time of informed consent through 60 days post end of treatment
Title
MEDI2228 clearance for PK
Description
To assess the pharmacokinetics of Medi2228
Time Frame
From time of informed consent through 60 days post end of treatment
Title
MEDI2228 terminal half-life for PK
Description
To assess the pharmacokinetics of MEDI2228
Time Frame
From time of informed consent through 60 days post end of treatment
Title
Number of subjects who develop anti-drug antibodies (ADAs)
Description
To assess immunogenicity of MEDI2228
Time Frame
From time of informed consents through 60 days post end of treatment
Title
Objective response rate (ORR)
Description
To assess the anti-tumor activity of MEDI2228
Time Frame
From time of informed consent and up to three years after final patient is enrolled
Title
Clinical benefit rate
Description
To assess clinical benefit of MEDI2228
Time Frame
From time of informed consent up to three years after final patient is enrolled
Title
Duration of response (DoR)
Description
To assess the anti-tumor activity of MEDI2228
Time Frame
From time of informed consent and up to three years after final patient is enrolled
Title
Progression free survival (PFS)
Description
To assess the anti-tumor activity of MEDI2228
Time Frame
From time of informed consent and up to three years after final patient is enrolled
Title
Overall Survival (OS)
Description
To assess the anti-tumor activity of MEDI2228
Time Frame
From time of informed consent and up to three years after final patient is enrolled
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
101 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must be ≥ 18 years of age at the time of screening.
Subjects must have a confirmed diagnosis of relapsed/refractory MM as per IMWG criteria (Rajkumar et al, 2014) and have exhausted standard of care regimens with proven clinical benefit, which include agents from the following anti myeloma therapies: PIs, IMIDs, and mAbs and have measurable disease with at least one of the following criteria:
Serum M-protein ≥ 0.5 g/dL
Urine M-protein ≥ 200 mg/24 hours
Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal.
Subjects must either be ineligible for or post-autologous stem cell transplant.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Adequate organ and marrow functions as determined per protocol-defined criteria.
Exclusion Criteria
Any of the following would exclude the subject from participation in the study:
Target Disease:
Subjects who have previously received an autologous stem cell transplant if less than 90 days have elapsed from the time of transplant or the subject has not recovered from transplant associated toxicities prior to the first scheduled dose of MEDI2228
Subjects who have previously received an allogeneic stem cell transplant
Central nervous system (CNS) involvement(including meningeal involvement) by MRI or cerebrospinal fluid exam
Known history of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome, plasma cell leukemia, Waldenstrom's macroglobulinemia, or amyloidosis
Medical History and Concurrent Diseases:
Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medimmune LLC
Organizational Affiliation
Sponsor GmbH
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Research Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Research Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Research Site
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Research Site
City
Melbourne
ZIP/Postal Code
3004
Country
Australia
Facility Name
Research Site
City
Athens
ZIP/Postal Code
11528
Country
Greece
Facility Name
Research Site
City
Badalona
ZIP/Postal Code
08916
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca/MedImmune group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Time Frame
AstraZeneca/MedImmune will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca/MedImmune will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Learn more about this trial
MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma
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