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Trial record 1 of 1 for:    NCT02549651
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MEDI4736 Alone and in Combination With Tremelimumab or AZD9150 in Adult Subjects With Relapsed/Refractory DLBCL (D4190C00023)

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ClinicalTrials.gov Identifier: NCT02549651
Recruitment Status : Completed
First Posted : September 15, 2015
Last Update Posted : February 27, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Drug: MEDI4736 Drug: tremelimumab Drug: AZD9150 Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : July 13, 2016
Actual Primary Completion Date : February 4, 2019
Actual Study Completion Date : February 4, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Durvalumab

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
  2. 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


Secondary Outcome Measures :
  1. Number of subjects who develop anti-drug antibodies (ADA) [ Time Frame: Screening through 90 days after last dose of study medication ]
  2. Time to Response [ Time Frame: Screening though 3 years after the last subject receives the first dose of study medication ]
  3. Duration of Response [ Time Frame: Screening though 3 years after the last subject receives the first dose of study medication ]
  4. Progression Free survival [ Time Frame: Screening though 3 years after the last subject receives the first dose of study medication ]
  5. Time to progression [ Time Frame: Screening though 3 years after the last subject receives the first dose of study medication ]
  6. Event free survival [ Time Frame: Screening though 3 years after the last subject receives the first dose of study medication ]
  7. Overall survival [ Time Frame: Screening though 3 years after the last subject receives the first dose of study medication ]
  8. MEDI4736 Maximum Plasma Concentration (Cmax) [ Time Frame: Measured at defined study visits from time of first dose through end of treatment ]
  9. Tremelimumab Maximum Plasma Concentration (Cmax) [ Time Frame: Measured at defined study visits from time of first dose through end of treatment ]
  10. AZD9150 Maximum Plasma Concentration (Cmax) [ Time Frame: Measured at defined study visits from time of first dose through end of treatment ]
  11. MEDI4736 Minimum Plasma Concentration (Cmin) [ Time Frame: Measured at defined study visits from time of first dose through end of treatment ]
  12. Tremelimumab Minimum Plasma Concentration (Cmin) [ Time Frame: Measured at defined study visits from time of first dose through end of treatment ]
  13. AZD9150 Minimum Plasma Concentration (Cmin) [ Time Frame: Measured at defined study visits from time of first dose through end of treatment ]
  14. 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) ]
  15. 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) ]
  16. 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) ]
  17. 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) ]
  18. Baseline PD-L1 protein expression within the tumor [ Time Frame: Measured on tumor samples provided at screening ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02549651


Locations
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United States, California
Research Site
La Jolla, California, United States, 92093
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21201
United States, New Mexico
Research Site
Albuquerque, New Mexico, United States, 87131
United States, North Carolina
Research Site
Durham, North Carolina, United States, 27710
United States, South Carolina
Research Site
Charleston, South Carolina, United States, 29425
United States, Texas
Research Site
Dallas, Texas, United States, 75390
Research Site
Houston, Texas, United States, 77030
United States, Wisconsin
Research Site
Milwaukee, Wisconsin, United States, 53226
France
Research Site
Marseille, France, 13273
Research Site
Villejuif, France, 94805
Ireland
Research Site
Dublin 8, Ireland
Research Site
Galway, Ireland
United Kingdom
Research Site
Leicester, United Kingdom, LE1 5WW
Sponsors and Collaborators
MedImmune LLC
Investigators
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Study Director: MedImmune LLC MedImmune LLC
More Information
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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02549651    
Other Study ID Numbers: D4190C00023
First Posted: September 15, 2015    Key Record Dates
Last Update Posted: February 27, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedImmune LLC:
DLBCL
MEDI4736
durvalumab
tremelimumab
AZD9150
 anti-PD-L1
anti-CTLA-4
immunotherapy
IMTC
STAT3
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Durvalumab
Tremelimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents