MEDI4736 Alone and in Combination With Tremelimumab or AZD9150 in Adult Subjects With Relapsed/Refractory DLBCL (D4190C00023)

February 26, 2019 updated by: MedImmune LLC

A Phase 1b Study to Evaluate the Safety and Efficacy of MEDI4736 as Monotherapy and in Combination With Tremelimumab or AZD9150 in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma.

The purpose of this study is to evaluate the safety, tolerability, and efficacy of MEDI4736 (durvalumab) alone and in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory dIffuse large B-cell lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, open-label, dose-escalation and dose-expansion study of MEDI4736 (durvalumab) as monotherapy or in combination with either tremelimumab or AZD9150. The objectives are to describe any dose-limiting toxicities, determine the maximum tolerated dose, and evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetics, and pharmacodynamics of MEDI4736 as monotherapy or in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory diffuse large B-cell lymphoma.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille, France, 13273
        • Research Site
      • Villejuif, France, 94805
        • Research Site
  • Ireland
      • Dublin 8, Ireland
        • Research Site
      • Galway, Ireland
        • Research Site
  • United Kingdom
      • Leicester, United Kingdom, LE1 5WW
        • Research Site
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Research Site
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Research Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Research Site
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Research Site
    • Texas
      • Dallas, Texas, United States, 75390
        • Research Site
      • Houston, Texas, United States, 77030
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Subjects with histologically confirmed relapsed or refractory DLBCL who have received at least 1 prior rituximab containing chemotherapy regimen but no more than 5 prior lines of therapy
  3. Eastern Cooperative Group (ECOG) performance status of 0 or 1
  4. Measurable disease by International Working Group (IWG) response criteria for lymphoma
  5. Adequate organ and marrow function

Exclusion Criteria:

  1. Previous immune-mediated therapy
  2. Subjects with prior ASCT or allogenic HCT. Subjects ineligible for available curative options after failing ASCT and have met the hematologic criteria are eligible to participate in this study. Subjects with prior allogenic HCT will be excluded.
  3. Documented current central nervous system involvement

3. Active or prior documented autoimmune or inflammatory disease within 3 years, with some exceptions 4. Concurrent or prior conventional or investigational anticancer therapy, within 28 days prior to the first dose of study medication(s)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MEDI4736
Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
Experimental: MEDI4736 and tremelimumab
Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
Drug: tremelimumab
Tremelimumab is an anti-CTLA4 monoclonal antibody (MAb) administered via intravenous infusion
Experimental: MEDI4736 and AZD9150
Drug: MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
Drug: AZD9150
AZD9150 is an antisense oligonucleotide (ASO) administered via intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events
Time Frame: Screening through 90 days after the last dose of study medication
Screening through 90 days after the last dose of study medication
Number of subjects experiencing dose-limiting toxicities
Time Frame: First dose of study medications through 28 days after the administration of MEDI4736 or MEDI4736 and tremelimumab, 35 days after administration of MEDI4736 and AZD9150
Changes from baseline in laboratory parameters, vital signs, and ECGs
First dose of study medications through 28 days after the administration of MEDI4736 or MEDI4736 and tremelimumab, 35 days after administration of MEDI4736 and AZD9150

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of subjects who develop anti-drug antibodies (ADA)
Time Frame: Screening through 90 days after last dose of study medication
Screening through 90 days after last dose of study medication
Time to Response
Time Frame: Screening though 3 years after the last subject receives the first dose of study medication
Screening though 3 years after the last subject receives the first dose of study medication
Duration of Response
Time Frame: Screening though 3 years after the last subject receives the first dose of study medication
Screening though 3 years after the last subject receives the first dose of study medication
Progression Free survival
Time Frame: Screening though 3 years after the last subject receives the first dose of study medication
Screening though 3 years after the last subject receives the first dose of study medication
Time to progression
Time Frame: Screening though 3 years after the last subject receives the first dose of study medication
Screening though 3 years after the last subject receives the first dose of study medication
Event free survival
Time Frame: Screening though 3 years after the last subject receives the first dose of study medication
Screening though 3 years after the last subject receives the first dose of study medication
Overall survival
Time Frame: Screening though 3 years after the last subject receives the first dose of study medication
Screening though 3 years after the last subject receives the first dose of study medication
MEDI4736 Maximum Plasma Concentration (Cmax)
Time Frame: Measured at defined study visits from time of first dose through end of treatment
Measured at defined study visits from time of first dose through end of treatment
Tremelimumab Maximum Plasma Concentration (Cmax)
Time Frame: Measured at defined study visits from time of first dose through end of treatment
Measured at defined study visits from time of first dose through end of treatment
AZD9150 Maximum Plasma Concentration (Cmax)
Time Frame: Measured at defined study visits from time of first dose through end of treatment
Measured at defined study visits from time of first dose through end of treatment
MEDI4736 Minimum Plasma Concentration (Cmin)
Time Frame: Measured at defined study visits from time of first dose through end of treatment
Measured at defined study visits from time of first dose through end of treatment
Tremelimumab Minimum Plasma Concentration (Cmin)
Time Frame: Measured at defined study visits from time of first dose through end of treatment
Measured at defined study visits from time of first dose through end of treatment
AZD9150 Minimum Plasma Concentration (Cmin)
Time Frame: Measured at defined study visits from time of first dose through end of treatment
Measured at defined study visits from time of first dose through end of treatment
Individual MEDI4736 Concentrations
Time Frame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Individual tremelimumab Concentrations
Time Frame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Individual AZD9150 Concentrations
Time Frame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Change from baseline of STAT3 RNA (signal transducer and activator of transcription)
Time Frame: Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months)
Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months)
Baseline PD-L1 protein expression within the tumor
Time Frame: Measured on tumor samples provided at screening
Measured on tumor samples provided at screening

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MedImmune LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 13, 2016

Primary Completion (Actual)

February 4, 2019

Study Completion (Actual)

February 4, 2019

Study Registration Dates

First Submitted

August 27, 2015

First Submitted That Met QC Criteria

September 11, 2015

First Posted (Estimate)

September 15, 2015

Study Record Updates

Last Update Posted (Actual)

February 27, 2019

Last Update Submitted That Met QC Criteria

February 26, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D4190C00023

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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