Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02117219
• Collaborator: (none)
• Enrollment: 67
• Locations: 21
• Arms: 3
• Actual Duration (Months): 59.3
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome	Biological: MEDI4736 Evaluate MEDI4736 in MDS; Drug: VIDAZA; Biological: tremelimumab	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 67 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 20, 2014
• Actual Primary Completion Date: Apr 30, 2019
• Actual Study Completion Date: Apr 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI4736 Evaluate MEDI4736 in MDS Evaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS	Biological: MEDI4736 Evaluate MEDI4736 in MDS; MEDI4736 will be administered by IV infusion; Other Names: durvalumab ; 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; Other Names: azacitidine
Experimental: MEDI4736 + tremelimumab Evaluate MEDI4736 in combination with tremelimumab	Biological: tremelimumab; tremelimumab will be administered by IV infusion
Experimental: MEDI4736 + tremelimumab + azacitidine Evaluate MEDI4736 in combination with tremelimumab and azacitidine	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; Other Names: azacitidine ; Biological: tremelimumab; tremelimumab will be administered by IV infusion

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. Clinical outcome in terms of response: duration of response [2 years]

   As defined by IWG 2006 MDS response criteria

2. Clinical outcome in terms of response: transfusion requirements [2 years]

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

3. Clinical outcome in terms of response: progression-free survival (PFS) [2 years]

   As defined by IWG 2006 MDS response criteria

4. Clinical outcome in terms of response: survival (OS) [2 years]

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

5. Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration [1 year]

   Peak concentration of MEDI4736 and tremelimumab in serum

6. Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve [1 year]

   Analysis of area under the concentration-time curve

7. Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance [1 year]

   Rate of MEDI4736 and tremelimumab clearance

8. Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life [1 year]

   MEDI4736 and tremelimumab concentration terminal half-life

9. Immunogenicity [1 year]

   Determine by number of subjects who develop ADA (anti-drug antibody).

10. 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)

11. Health-related quality of life (QOL): pain (Part 1 only) [2 years]

    Analysis of incidence of pain reporting (Part 1 only)

12. Health-related quality of life (QOL): health status (Part 1 only) [2 years]

    Analysis of reporting of health status. (Part 1 only)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Scottsdale	Arizona	United States	85259
2	Research Site	Los Angeles	California	United States	90095
3	Research Site	New Haven	Connecticut	United States	06520-8063
4	Research Site	Tampa	Florida	United States	33612
5	Research Site	Atlanta	Georgia	United States	30322
6	Research Site	Chicago	Illinois	United States	60637
7	Research Site	Baltimore	Maryland	United States	21201
8	Research Site	Boston	Massachusetts	United States	02215
9	Research Site	Detroit	Michigan	United States	48201
10	Research Site	Rochester	Minnesota	United States	55905
11	Research Site	New York	New York	United States	10029
12	Research Site	New York	New York	United States	10065
13	Research Site	Greenville	South Carolina	United States	29601
14	Research Site	Houston	Texas	United States	77030
15	Research Site	San Antonio	Texas	United States	78229
16	Research Site	Milwaukee	Wisconsin	United States	53226
17	Research Site	Paris Cedex 10		France	75475
18	Research Site	Dresden		Germany	1307
19	Research Site	Brighton		United Kingdom	BN2 5BE
20	Research Site	London		United Kingdom	SE5 9RS
21	Research Site	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• MedImmune LLC

Investigators

• Study Director: MedImmune LLC, MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT02117219
• Other Study ID Numbers: D4190C00007
• First Posted: Apr 17, 2014
• Last Update Posted: May 10, 2019
• Last Verified: May 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by MedImmune LLC: Myelodysplastic syndrome; MDS
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Azacitidine; Durvalumab; Tremelimumab

Study Results

No Results Posted as of May 10, 2019