Relapsed/Refractory Multiple Myeloma
Conditions
Keywords
multiple myeloma, relapsed/refractory, open-label
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.
Interventions
BIOLOGICALDose Escalation, MEDI2228, ADC (antibody drug conjugate)
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
BIOLOGICALDose Expansion, MEDI2228, ADC (antibody drug conjugate)
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.
Sponsors
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to 101 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects must be ≥ 18 years of age at the time of screening. 2. 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: 1. Serum M-protein ≥ 0.5 g/dL 2. Urine M-protein ≥ 200 mg/24 hours 3. Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal. 3. Subjects must either be ineligible for or post-autologous stem cell transplant. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 5. 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: 1. 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 2. Subjects who have previously received an allogeneic stem cell transplant 3. Central nervous system (CNS) involvement(including meningeal involvement) by MRI or cerebrospinal fluid exam 4. 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: 5. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of adverse events (AEs) | From time of informed consent through 90 days post end of treatment | To assess by the occurrence of adverse events (AEs) |
| Occurrence of SAE (serious adverse events) | From time of informed consent through 90 days post end of treatment | To assess the occurrence of serious adverse events (SAEs) |
| Occurrence of DLTs (dose limiting toxicities) | From time of informed consent through 90 days post end of treatment | 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 | From time of informed consent and up to 21 days post end of treatment | To assess serum chemistry, hematology, coagulation and urninalysis |
| Number of patients with changes in vital signs from baseline | From time of informed consent and up to 21 days post end of treatment | To assess body temperature, blood pressure and heart rate |
| Number of patients with changes in elctrocardiogram (ECG) results from baseline | From time of informed consent and up to 21 days post end of treatment | To assess using 12 lead ECG recordings |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical benefit rate | From time of informed consent up to three years after final patient is enrolled | To assess clinical benefit of MEDI2228 |
| Duration of response (DoR) | From time of informed consent and up to three years after final patient is enrolled | To assess the anti-tumor activity of MEDI2228 |
| MEDI2228 maximum observed concentration for PK | From time of informed consent through 60 days post end of treatment | To assess the pharmacokinetics of MEDI2228 |
| Overall Survival (OS) | From time of informed consent and up to three years after final patient is enrolled | To assess the anti-tumor activity of MEDI2228 |
| Progression free survival (PFS) | From time of informed consent and up to three years after final patient is enrolled | To assess the anti-tumor activity of MEDI2228 |
| MEDI2228 area under the concentration-time curve for PK | From time of informed consent through 60 days post end of treatment | To assess the pharmacokinetics of MEDI2228 |
| MEDI2228 clearance for PK | From time of informed consent through 60 days post end of treatment | To assess the pharmacokinetics of Medi2228 |
| MEDI2228 terminal half-life for PK | From time of informed consent through 60 days post end of treatment | To assess the pharmacokinetics of MEDI2228 |
| Number of subjects who develop anti-drug antibodies (ADAs) | From time of informed consents through 60 days post end of treatment | To assess immunogenicity of MEDI2228 |
| Objective response rate (ORR) | From time of informed consent and up to three years after final patient is enrolled | To assess the anti-tumor activity of MEDI2228 |
Countries
Australia, Greece, Spain, United States
Outcome results
None listed