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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

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02117219
Enrollment
67
Registered
2014-04-17
Start date
2014-05-20
Completion date
2019-04-30
Last updated
2019-05-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Myelodysplastic Syndrome

Keywords

Myelodysplastic syndrome, MDS

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.

Interventions

BIOLOGICALMEDI4736 Evaluate MEDI4736 in MDS

MEDI4736 will be administered by IV infusion

DRUGVIDAZA

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

BIOLOGICALtremelimumab

tremelimumab will be administered by IV infusion

Sponsors

MedImmune LLC
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frameDescription
Subject's safety where no more than one out of six subjects experience DLTs at a given dose180 daysDLT (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)730 daysOverall 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

MeasureTime frameDescription
Clinical outcome in terms of response: progression-free survival (PFS)2 yearsAs defined by IWG 2006 MDS response criteria
Clinical outcome in terms of response: survival (OS)2 yearsAs defined by IWG 2006 MDS response criteria and collection of survival data
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration1 yearPeak concentration of MEDI4736 and tremelimumab in serum
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve1 yearAnalysis of area under the concentration-time curve
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance1 yearRate of MEDI4736 and tremelimumab clearance
Clinical outcome in terms of response: duration of response2 yearsAs defined by IWG 2006 MDS response criteria
Immunogenicity1 yearDetermine by number of subjects who develop ADA (anti-drug antibody).
Health-related quality of life (QOL): disease- and treatment-related symptoms (Part 1 only)2 yearsAnalysis of reporting of disease- and treatment-related symptoms (Part 1 only)
Health-related quality of life (QOL): pain (Part 1 only)2 yearsAnalysis of incidence of pain reporting (Part 1 only)
Health-related quality of life (QOL): health status (Part 1 only)2 yearsAnalysis of reporting of health status. (Part 1 only)
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life1 yearMEDI4736 and tremelimumab concentration terminal half-life
Clinical outcome in terms of response: transfusion requirements2 yearsAs defined by IWG 2006 MDS response criteria and incidence of transfusions.

Countries

France, Germany, United Kingdom, United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 4, 2026