Clinical trial NCT02117219: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Myelodysplastic Syndrome
Keywords: Myelodysplastic syndrome
MDS
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2014-04-17
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Subject's safety where no more than one out of six subjects experience DLTs at a given dose
timeFrame: 180 days
measure: Subject's safety overall (monotherapy and combination therapies)
timeFrame: 730 days
Secondary outcomes:
measure: Clinical outcome in terms of response: duration of response
timeFrame: 2 years
measure: Clinical outcome in terms of response: transfusion requirements
timeFrame: 2 years
measure: Clinical outcome in terms of response: progression-free survival (PFS)
timeFrame: 2 years
measure: Clinical outcome in terms of response: survival (OS)
timeFrame: 2 years
measure: Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration
timeFrame: 1 year
measure: Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve
timeFrame: 1 year
measure: Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance
timeFrame: 1 year
measure: Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life
timeFrame: 1 year
measure: Immunogenicity
timeFrame: 1 year
measure: Health-related quality of life (QOL): disease- and treatment-related symptoms (Part 1 only)
timeFrame: 2 years
measure: Health-related quality of life (QOL): pain (Part 1 only)
timeFrame: 2 years
measure: Health-related quality of life (QOL): health status (Part 1 only)
timeFrame: 2 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Paris Cedex 10
country: France
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Brighton
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References: