Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome
- Conditions
- Myelodysplastic Syndrome
- Interventions
- Registration Number
- NCT02117219
- Lead Sponsor
- MedImmune LLC
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 67
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.
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MEDI4736 + tremelimumab + azacitidine tremelimumab Evaluate MEDI4736 in combination with tremelimumab and azacitidine MEDI4736 Evaluate MEDI4736 in MDS MEDI4736 Evaluate MEDI4736 in MDS Evaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS MEDI4736 Evaluate MEDI4736 in MDS VIDAZA Evaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS MEDI4736 + tremelimumab tremelimumab Evaluate MEDI4736 in combination with tremelimumab MEDI4736 + tremelimumab + azacitidine VIDAZA Evaluate MEDI4736 in combination with tremelimumab and azacitidine
- Primary Outcome Measures
Name Time Method Subject's safety where no more than one out of six subjects experience DLTs at a given dose 180 days 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) 730 days 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
Name Time Method Clinical outcome in terms of response: survival (OS) 2 years As defined by IWG 2006 MDS response criteria and collection of survival data
Clinical outcome in terms of response: progression-free survival (PFS) 2 years As defined by IWG 2006 MDS response criteria
Clinical outcome in terms of response: duration of response 2 years As defined by IWG 2006 MDS response criteria
Clinical outcome in terms of response: transfusion requirements 2 years As defined by IWG 2006 MDS response criteria and incidence of transfusions.
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration 1 year Peak concentration of MEDI4736 and tremelimumab in serum
Health-related quality of life (QOL): health status (Part 1 only) 2 years Analysis of reporting of health status. (Part 1 only)
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve 1 year Analysis of area under the concentration-time curve
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance 1 year Rate of MEDI4736 and tremelimumab clearance
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life 1 year MEDI4736 and tremelimumab concentration terminal half-life
Health-related quality of life (QOL): pain (Part 1 only) 2 years Analysis of incidence of pain reporting (Part 1 only)
Immunogenicity 1 year 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) 2 years Analysis of reporting of disease- and treatment-related symptoms (Part 1 only)
Trial Locations
- Locations (1)
Research Site
🇬🇧Manchester, United Kingdom