Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome

A Phase 1 Study to Evaluate the Safety and Tolerability of MEDI4736 as Monotherapy or in Combination With Tremelimumab With or Without Azacitidine in Subjects With Myelodysplastic Syndrome After Treatment With Hypomethylating Agents

This is a multicenter, open-label, Phase 1 study to assess the safety and antitumor activity of MEDI4736 as Monotherapy or in Combination with Tremelimumab with or without Azacitidine in Subjects with myelodysplastic syndrome after treatment with hypomethylating agents

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Biological: MEDI4736 Evaluate MEDI4736 in MDS; Drug: VIDAZA; Biological: tremelimumab

Detailed Description

A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death-1 ligand 1 [PD-L1]) to evaluate the safety, tolerability, PK, IM, and antitumor activity of MEDI4736 as monotherapy or in combination with Tremelimumab with or without Azacitidine in adult patients with myelodysplastic syndrome.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris Cedex 10, France, 75475
    • Research Site
• Germany
  • Dresden, Germany, 1307
    • Research Site
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Research Site
  • California
    • Los Angeles, California, United States, 90095
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8063
      • Research Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Research Site
    • New York, New York, United States, 10029
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Adult male or female subjects with pathologically confirmed MDS who failed to respond, relapsed after an initial response, or were unable to tolerate hypomethylating agents, ECOG performance status of 0 - 2, and adequate organ and marrow function.

Exclusion Criteria:

Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment, prior MAb against CTLA-4, PD-1, or PD-L1, alllogenic or haploidentical transplant, current immunosuppressive medication or autoimmune or inflammatory disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MEDI4736 Evaluate MEDI4736 in MDS; Evaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS	Biological: MEDI4736 Evaluate MEDI4736 in MDS; MEDI4736 will be administered by IV infusion; Other Names: durvalumab; Drug: VIDAZA; VIDAZA will be administered subcutaneously as described on the package insert VIDAZA will be administered in combination with MEDI4736 upon progression from MEDI4736 monotherapy; Other Names: azacitidine
EXPERIMENTAL: MEDI4736 + tremelimumab; Evaluate MEDI4736 in combination with tremelimumab	Biological: tremelimumab; tremelimumab will be administered by IV infusion
EXPERIMENTAL: MEDI4736 + tremelimumab + azacitidine; Evaluate MEDI4736 in combination with tremelimumab and azacitidine	Drug: VIDAZA; VIDAZA will be administered subcutaneously as described on the package insert VIDAZA will be administered in combination with MEDI4736 upon progression from MEDI4736 monotherapy; Other Names: azacitidine; Biological: tremelimumab; tremelimumab will be administered by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject's safety where no more than one out of six subjects experience DLTs at a given dose	DLT (MEDI4736 monotherapy only) assessment will be done by reviewing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results. For monotherapy or combo w/aza AEs, SAEs, lab evaluations, vital signs, physical exams, ECGs will be done.	180 days
Subject's safety overall (monotherapy and combination therapies)	Overall safety assessments will be done by reviewing adverse events (AEs, serious adverse events (SAEs), laboratory evaluations, vital signs, physical examinations and electrocardiogram (ECG) results.	730 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical outcome in terms of response: duration of response	As defined by IWG 2006 MDS response criteria	2 years
Clinical outcome in terms of response: transfusion requirements	As defined by IWG 2006 MDS response criteria and incidence of transfusions.	2 years
Clinical outcome in terms of response: progression-free survival (PFS)	As defined by IWG 2006 MDS response criteria	2 years
Clinical outcome in terms of response: survival (OS)	As defined by IWG 2006 MDS response criteria and collection of survival data	2 years
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration	Peak concentration of MEDI4736 and tremelimumab in serum	1 year
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve	Analysis of area under the concentration-time curve	1 year
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance	Rate of MEDI4736 and tremelimumab clearance	1 year
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life	MEDI4736 and tremelimumab concentration terminal half-life	1 year
Immunogenicity	Determine by number of subjects who develop ADA (anti-drug antibody).	1 year
Health-related quality of life (QOL): disease- and treatment-related symptoms (Part 1 only)	Analysis of reporting of disease- and treatment-related symptoms (Part 1 only)	2 years
Health-related quality of life (QOL): pain (Part 1 only)	Analysis of incidence of pain reporting (Part 1 only)	2 years
Health-related quality of life (QOL): health status (Part 1 only)	Analysis of reporting of health status. (Part 1 only)	2 years

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 20, 2014
• Primary Completion (ACTUAL): April 30, 2019
• Study Completion (ACTUAL): April 30, 2019

Study Registration Dates

• First Submitted: April 14, 2014
• First Submitted That Met QC Criteria: April 15, 2014
• First Posted (ESTIMATE): April 17, 2014

Study Record Updates

• Last Update Posted (ACTUAL): May 10, 2019
• Last Update Submitted That Met QC Criteria: May 9, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: MDS; Myelodysplastic syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab; Azacitidine
• Other Study ID Numbers: D4190C00007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No