NCT03489525

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
107

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started May 2018

Longer than P75 for phase_1

Geographic Reach
4 countries

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 17, 2018

Completed
19 days until next milestone

First Posted

Study publicly available on registry

April 5, 2018

Completed
1 month until next milestone

Study Start

First participant enrolled

May 8, 2018

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 21, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 21, 2022

Completed
Last Updated

March 28, 2022

Status Verified

March 1, 2022

Enrollment Period

3.9 years

First QC Date

March 17, 2018

Last Update Submit

March 25, 2022

Conditions

Relapsed/Refractory Multiple Myeloma

Keywords

multiple myelomarelapsed/refractoryopen-label

Outcome Measures

Primary Outcomes (6)

  • Occurrence of adverse events (AEs)

    To assess by the occurrence of adverse events (AEs)

    From time of informed consent through 90 days post end of treatment

  • Occurrence of SAE (serious adverse events)

    To assess the occurrence of serious adverse events (SAEs)

    From time of informed consent through 90 days post end of treatment

  • Occurrence of DLTs (dose limiting toxicities)

    To assess by the occurrence of hematologic and non-hematologic toxicities, AEs, and abnormal laboratory results

    From time of informed consent through 90 days post end of treatment

  • Number of patients with changes in laboratory parameters from baseline

    To assess serum chemistry, hematology, coagulation and urninalysis

    From time of informed consent and up to 21 days post end of treatment

  • Number of patients with changes in vital signs from baseline

    To assess body temperature, blood pressure and heart rate

    From time of informed consent and up to 21 days post end of treatment

  • Number of patients with changes in elctrocardiogram (ECG) results from baseline

    To assess using 12 lead ECG recordings

    From time of informed consent and up to 21 days post end of treatment

Secondary Outcomes (10)

  • MEDI2228 maximum observed concentration for PK

    From time of informed consent through 60 days post end of treatment

  • MEDI2228 area under the concentration-time curve for PK

    From time of informed consent through 60 days post end of treatment

  • MEDI2228 clearance for PK

    From time of informed consent through 60 days post end of treatment

  • MEDI2228 terminal half-life for PK

    From time of informed consent through 60 days post end of treatment

  • Number of subjects who develop anti-drug antibodies (ADAs)

    From time of informed consents through 60 days post end of treatment

  • +5 more secondary outcomes

Study Arms (2)

Dose Escalation, MEDI2228, ADC

EXPERIMENTAL

Single agent MEDI2228, ADC (antibody drug conjugate) will be administered to adult subjects with relapsed/refractory (R/R) multiple myeloma (MM).

Biological: Dose Escalation, MEDI2228, ADC (antibody drug conjugate)

Dose Expansion, MEDI2228, ADC

EXPERIMENTAL

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.

Biological: Dose Expansion, MEDI2228, ADC (antibody drug conjugate)

Interventions

Dose Escalation, MEDI2228, ADC (antibody drug conjugate)BIOLOGICAL

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

Dose Escalation, MEDI2228, ADC
Dose Expansion, MEDI2228, ADC (antibody drug conjugate)BIOLOGICAL

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.

Dose Expansion, MEDI2228, ADC

Eligibility Criteria

Age18 Years - 101 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Research Site

Phoenix, Arizona, 85054, United States

Location

Research Site

Jacksonville, Florida, 32224, United States

Location

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

Detroit, Michigan, 48201, United States

Location

Research Site

Rochester, Minnesota, 55905, United States

Location

Research Site

Charlotte, North Carolina, 28204, United States

Location

Research Site

Fairfax, Virginia, 22031, United States

Location

Research Site

Melbourne, 3004, Australia

Location

Research Site

Athens, 11528, Greece

Location

Research Site

Badalona, 08916, Spain

Location

MeSH Terms

Conditions

Multiple MyelomaRecurrence

Interventions

arginine decarboxylaseImmunoconjugates

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AntibodiesImmunoglobulinsSerum GlobulinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsGlobulinsImmunologic FactorsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and Uses

Study Officials

  • Medimmune LLC

    Sponsor GmbH

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Masking Details
Open-label
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 17, 2018

First Posted

April 5, 2018

Study Start

May 8, 2018

Primary Completion

March 21, 2022

Study Completion

March 21, 2022

Last Updated

March 28, 2022

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will share

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.

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.
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.

Locations

US(8)AU(1)ES(1)GR(1)