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Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome

Primary Purpose

Myelodysplastic Syndrome

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MEDI4736 Evaluate MEDI4736 in MDS
VIDAZA
tremelimumab
Sponsored by
MedImmune LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring Myelodysplastic syndrome, MDS

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

MEDI4736 Evaluate MEDI4736 in MDS

MEDI4736 + tremelimumab

MEDI4736 + tremelimumab + azacitidine

Arm Description

Evaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS

Evaluate MEDI4736 in combination with tremelimumab

Evaluate MEDI4736 in combination with tremelimumab and azacitidine

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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

Full Information

First Posted
April 14, 2014
Last Updated
May 9, 2019
Sponsor
MedImmune LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02117219
Brief Title
Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
May 20, 2014 (Actual)
Primary Completion Date
April 30, 2019 (Actual)
Study Completion Date
April 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome
Keywords
Myelodysplastic syndrome, MDS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MEDI4736 Evaluate MEDI4736 in MDS
Arm Type
Experimental
Arm Description
Evaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS
Arm Title
MEDI4736 + tremelimumab
Arm Type
Experimental
Arm Description
Evaluate MEDI4736 in combination with tremelimumab
Arm Title
MEDI4736 + tremelimumab + azacitidine
Arm Type
Experimental
Arm Description
Evaluate MEDI4736 in combination with tremelimumab and azacitidine
Intervention Type
Biological
Intervention Name(s)
MEDI4736 Evaluate MEDI4736 in MDS
Other Intervention Name(s)
durvalumab
Intervention Description
MEDI4736 will be administered by IV infusion
Intervention Type
Drug
Intervention Name(s)
VIDAZA
Other Intervention Name(s)
azacitidine
Intervention Description
VIDAZA will be administered subcutaneously as described on the package insert VIDAZA will be administered in combination with MEDI4736 upon progression from MEDI4736 monotherapy
Intervention Type
Biological
Intervention Name(s)
tremelimumab
Intervention Description
tremelimumab will be administered by IV infusion
Primary Outcome Measure Information:
Title
Subject's safety where no more than one out of six subjects experience DLTs at a given dose
Description
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.
Time Frame
180 days
Title
Subject's safety overall (monotherapy and combination therapies)
Description
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.
Time Frame
730 days
Secondary Outcome Measure Information:
Title
Clinical outcome in terms of response: duration of response
Description
As defined by IWG 2006 MDS response criteria
Time Frame
2 years
Title
Clinical outcome in terms of response: transfusion requirements
Description
As defined by IWG 2006 MDS response criteria and incidence of transfusions.
Time Frame
2 years
Title
Clinical outcome in terms of response: progression-free survival (PFS)
Description
As defined by IWG 2006 MDS response criteria
Time Frame
2 years
Title
Clinical outcome in terms of response: survival (OS)
Description
As defined by IWG 2006 MDS response criteria and collection of survival data
Time Frame
2 years
Title
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration
Description
Peak concentration of MEDI4736 and tremelimumab in serum
Time Frame
1 year
Title
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve
Description
Analysis of area under the concentration-time curve
Time Frame
1 year
Title
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance
Description
Rate of MEDI4736 and tremelimumab clearance
Time Frame
1 year
Title
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life
Description
MEDI4736 and tremelimumab concentration terminal half-life
Time Frame
1 year
Title
Immunogenicity
Description
Determine by number of subjects who develop ADA (anti-drug antibody).
Time Frame
1 year
Title
Health-related quality of life (QOL): disease- and treatment-related symptoms (Part 1 only)
Description
Analysis of reporting of disease- and treatment-related symptoms (Part 1 only)
Time Frame
2 years
Title
Health-related quality of life (QOL): pain (Part 1 only)
Description
Analysis of incidence of pain reporting (Part 1 only)
Time Frame
2 years
Title
Health-related quality of life (QOL): health status (Part 1 only)
Description
Analysis of reporting of health status. (Part 1 only)
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MedImmune LLC
Organizational Affiliation
MedImmune LLC
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Research Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520-8063
Country
United States
Facility Name
Research Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29601
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Research Site
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
Research Site
City
Dresden
ZIP/Postal Code
1307
Country
Germany
Facility Name
Research Site
City
Brighton
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Research Site
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome

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