Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome

Myelodysplastic Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02117219
• Other study ID #: D4190C00007
• Status: Completed
• Phase: Phase 1
• Start date: May 20, 2014
• Est. completion date: April 30, 2019

Study information

• Verified date: May 2019
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: April 30, 2019
• Est. primary completion date: April 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Biological:
• MEDI4736 Evaluate MEDI4736 in MDS
MEDI4736 will be administered by IV infusion

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

Biological:
• tremelimumab
tremelimumab will be administered by IV infusion

Locations

Country	Name	City	State
France	Research Site	Paris Cedex 10
Germany	Research Site	Dresden
United Kingdom	Research Site	Brighton
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United States	Research Site	Atlanta	Georgia
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chicago	Illinois
United States	Research Site	Detroit	Michigan
United States	Research Site	Greenville	South Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Los Angeles	California
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Rochester	Minnesota
United States	Research Site	San Antonio	Texas
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  France,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	180 days
Primary	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.	730 days
Secondary	Clinical outcome in terms of response: duration of response	As defined by IWG 2006 MDS response criteria	2 years
Secondary	Clinical outcome in terms of response: transfusion requirements	As defined by IWG 2006 MDS response criteria and incidence of transfusions.	2 years
Secondary	Clinical outcome in terms of response: progression-free survival (PFS)	As defined by IWG 2006 MDS response criteria	2 years
Secondary	Clinical outcome in terms of response: survival (OS)	As defined by IWG 2006 MDS response criteria and collection of survival data	2 years
Secondary	Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration	Peak concentration of MEDI4736 and tremelimumab in serum	1 year
Secondary	Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve	Analysis of area under the concentration-time curve	1 year
Secondary	Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance	Rate of MEDI4736 and tremelimumab clearance	1 year
Secondary	Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life	MEDI4736 and tremelimumab concentration terminal half-life	1 year
Secondary	Immunogenicity	Determine by number of subjects who develop ADA (anti-drug antibody).	1 year
Secondary	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)	2 years
Secondary	Health-related quality of life (QOL): pain (Part 1 only)	Analysis of incidence of pain reporting (Part 1 only)	2 years
Secondary	Health-related quality of life (QOL): health status (Part 1 only)	Analysis of reporting of health status. (Part 1 only)	2 years