Clinical trial NCT03489525: MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed/Refractory Multiple Myeloma
Keywords: multiple myeloma
relapsed/refractory
open-label
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2018-04-05
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of adverse events (AEs)
timeFrame: From time of informed consent through 90 days post end of treatment
measure: Occurrence of SAE (serious adverse events)
timeFrame: From time of informed consent through 90 days post end of treatment
measure: Occurrence of DLTs (dose limiting toxicities)
timeFrame: From time of informed consent through 90 days post end of treatment
measure: Number of patients with changes in laboratory parameters from baseline
timeFrame: From time of informed consent and up to 21 days post end of treatment
measure: Number of patients with changes in vital signs from baseline
timeFrame: From time of informed consent and up to 21 days post end of treatment
measure: Number of patients with changes in elctrocardiogram (ECG) results from baseline
timeFrame: From time of informed consent and up to 21 days post end of treatment
Secondary outcomes:
measure: MEDI2228 maximum observed concentration for PK
timeFrame: From time of informed consent through 60 days post end of treatment
measure: MEDI2228 area under the concentration-time curve for PK
timeFrame: From time of informed consent through 60 days post end of treatment
measure: MEDI2228 clearance for PK
timeFrame: From time of informed consent through 60 days post end of treatment
measure: MEDI2228 terminal half-life for PK
timeFrame: From time of informed consent through 60 days post end of treatment
measure: Number of subjects who develop anti-drug antibodies (ADAs)
timeFrame: From time of informed consents through 60 days post end of treatment
measure: Objective response rate (ORR)
timeFrame: From time of informed consent and up to three years after final patient is enrolled
measure: Clinical benefit rate
timeFrame: From time of informed consent up to three years after final patient is enrolled
measure: Duration of response (DoR)
timeFrame: From time of informed consent and up to three years after final patient is enrolled
measure: Progression free survival (PFS)
timeFrame: From time of informed consent and up to three years after final patient is enrolled
measure: Overall Survival (OS)
timeFrame: From time of informed consent and up to three years after final patient is enrolled
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Melbourne
country: Australia
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
Study officials:
affiliation: Sponsor GmbH
name: Medimmune LLC
role: STUDY_DIRECTOR
References: