Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome

MedImmune LLC67 enrolled

Overview

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

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Myelodysplastic Syndrome

Interventions

MEDI4736 Evaluate MEDI4736 in MDSBIOLOGICAL

MEDI4736 will be administered by IV infusion

VIDAZADRUG

VIDAZA will be administered subcutaneously as described on the package insert VIDAZA will be administered in combination with MEDI4736 upon progression from MEDI4736 monotherapy

tremelimumabBIOLOGICAL

tremelimumab will be administered by IV infusion

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

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.

Locations (21)

Research Site

Scottsdale, Arizona, United States

Research Site

Los Angeles, California, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 730 days

Secondary Outcomes

Clinical outcome in terms of response: duration of response

As defined by IWG 2006 MDS response criteria

Time frame: 2 years

Clinical outcome in terms of response: transfusion requirements

As defined by IWG 2006 MDS response criteria and incidence of transfusions.

Time frame: 2 years

Clinical outcome in terms of response: progression-free survival (PFS)

As defined by IWG 2006 MDS response criteria

Time frame: 2 years

Clinical outcome in terms of response: survival (OS)

As defined by IWG 2006 MDS response criteria and collection of survival data

Time frame: 2 years

Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration

Data from ClinicalTrials.gov

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