Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by MedImmune LLC
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT02117219
First received: April 14, 2014
Last updated: July 20, 2016
Last verified: July 2016
  Purpose
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 Intervention Phase
Myelodysplastic Syndrome
Biological: MEDI4736 Evaluate MEDI4736 in MDS
Drug: VIDAZA
Biological: tremelimumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Subject's safety where no more than one out of six subjects experience DLTs at a given dose [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 730 days ] [ Designated as safety issue: Yes ]
    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:
  • Clinical outcome in terms of response: duration of response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    As defined by IWG 2006 MDS response criteria

  • Clinical outcome in terms of response: transfusion requirements [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    As defined by IWG 2006 MDS response criteria and incidence of transfusions.

  • Clinical outcome in terms of response: progression-free survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    As defined by IWG 2006 MDS response criteria

  • Clinical outcome in terms of response: survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    As defined by IWG 2006 MDS response criteria and collection of survival data

  • Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Peak concentration of MEDI4736 and tremelimumab in serum

  • Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Analysis of area under the concentration-time curve

  • Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Rate of MEDI4736 and tremelimumab clearance

  • Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    MEDI4736 and tremelimumab concentration terminal half-life

  • Immunogenicity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Analysis of reporting of disease- and treatment-related symptoms (Part 1 only)

  • Health-related quality of life (QOL): pain (Part 1 only) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Analysis of incidence of pain reporting (Part 1 only)

  • Health-related quality of life (QOL): health status (Part 1 only) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Analysis of reporting of health status. (Part 1 only)


Estimated Enrollment: 76
Study Start Date: May 2014
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: azacitidine
Biological: tremelimumab
tremelimumab will be administered by IV infusion

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.
  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02117219

Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service 1-877-400-4656 AstraZeneca@emergingmed.com

  Show 18 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: MedImmune LLC MedImmune LLC
  More Information

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02117219     History of Changes
Other Study ID Numbers: D4190C00007 
Study First Received: April 14, 2014
Last Updated: July 20, 2016
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Keywords provided by MedImmune LLC:
Myelodysplastic syndrome
MDS

Additional relevant MeSH terms:
Syndrome
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
Tremelimumab
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2016