Myelodysplastic SyndromePhase 1NCT02117219
Phase 1 Study to Evaluate MEDI4736 in Subjects With Myelodysplastic Syndrome
A Phase 1 study testing MEDI4736 Evaluate MEDI4736 in MDS, VIDAZA and tremelimumab in people with Myelodysplastic Syndrome, run by MedImmune LLC at 21 sites in 4 countries.
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 Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- MEDI4736 Evaluate MEDI4736 in MDS, VIDAZA and tremelimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 21 sitesin 4 countries
- Study dates
- 20 May 2014to 30 Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
21 sites in 4 countries.
21 sites in 4 countries
United States16 sites
Research Site
Atlanta, Georgia, 30322
Research Site
Baltimore, Maryland, 21201
Research Site
Boston, Massachusetts, 02215
Research Site
Chicago, Illinois, 60637
Research Site
Detroit, Michigan, 48201
Research Site
Greenville, South Carolina, 29601
Research Site
Houston, Texas, 77030
Research Site
Los Angeles, California, 90095
Research Site
Milwaukee, Wisconsin, 53226
Research Site
New Haven, Connecticut, 06520-8063
Research Site
New York, New York, 10029
Research Site
New York, New York, 10065
Research Site
Rochester, Minnesota, 55905
Research Site
San Antonio, Texas, 78229
Research Site
Scottsdale, Arizona, 85259
Research Site
Tampa, Florida, 33612
United Kingdom3 sites
Research Site
Brighton, BN2 5BE
Research Site
London, SE5 9RS
Research Site
Manchester, M20 4BX
About this study
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
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
Read the 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.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- MEDI4736 Evaluate MEDI4736 in MDS, VIDAZA, tremelimumab
- Keywords
- Myelodysplastic syndrome, MDS
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI4736 Evaluate MEDI4736 in MDSBiological
Also called durvalumab
MEDI4736 will be administered by IV infusion
VIDAZADrug
Also called azacitidine
VIDAZA will be administered subcutaneously as described on the package insert VIDAZA will be administered in combination with MEDI4736 upon progression from MEDI4736 monotherapy
tremelimumabBiological
tremelimumab will be administered by IV infusion
| Study group | Role | What they receive |
|---|---|---|
| MEDI4736 Evaluate MEDI4736 in MDS | Experimental | Evaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS Receives: Biological: MEDI4736 Evaluate MEDI4736 in MDS; Drug: VIDAZA |
| MEDI4736 + tremelimumab | Experimental | Evaluate MEDI4736 in combination with tremelimumab Receives: Biological: tremelimumab |
| MEDI4736 + tremelimumab + azacitidine | Experimental | Evaluate MEDI4736 in combination with tremelimumab and azacitidine Receives: Drug: VIDAZA; Biological: tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 180 days
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.
Measured: 730 days
Secondary outcomes (12)
Clinical outcome in terms of response: duration of response
As defined by IWG 2006 MDS response criteria
Measured: 2 years
Clinical outcome in terms of response: transfusion requirements
As defined by IWG 2006 MDS response criteria and incidence of transfusions.
Measured: 2 years
Clinical outcome in terms of response: progression-free survival (PFS)
As defined by IWG 2006 MDS response criteria
Measured: 2 years
Clinical outcome in terms of response: survival (OS)
As defined by IWG 2006 MDS response criteria and collection of survival data
Measured: 2 years
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration
Peak concentration of MEDI4736 and tremelimumab in serum
Measured: 1 year
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve
Analysis of area under the concentration-time curve
Measured: 1 year
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance
Rate of MEDI4736 and tremelimumab clearance
Measured: 1 year
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life
MEDI4736 and tremelimumab concentration terminal half-life
Measured: 1 year
Immunogenicity
Determine by number of subjects who develop ADA (anti-drug antibody).
Measured: 1 year
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)
Measured: 2 years
Health-related quality of life (QOL): pain (Part 1 only)
Analysis of incidence of pain reporting (Part 1 only)
Measured: 2 years
Health-related quality of life (QOL): health status (Part 1 only)
Analysis of reporting of health status. (Part 1 only)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2014 (estimated)
- Study start20 May 2014
- Primary completion30 Apr 2019
- Study completion30 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MedImmune LLC, Study director, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02117219
- Sponsor's protocol ID
- D4190C00007
- Status last verified
- May 2019
- First submitted
- 14 Apr 2014
- Last updated
- 10 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02117219
- Acronym / sponsor ID
- D4190C00007
- Conditions
- Myelodysplastic Syndrome
- Keywords
- Myelodysplastic syndrome, MDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 20 May 2014 (actual)
- Primary completion
- 30 Apr 2019 (actual)
- Study completion
- 30 Apr 2019 (actual)
- First posted
- 17 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MEDI4736 Evaluate MEDI4736 in MDS | Experimental | Biological: MEDI4736 Evaluate MEDI4736 in MDS, Drug: VIDAZAEvaluate MEDI4736 monotherapy and MEDI4736 in combination with azacitidine after monotherapy progression in MDS |
| MEDI4736 + tremelimumab | Experimental | Biological: tremelimumabEvaluate MEDI4736 in combination with tremelimumab |
| MEDI4736 + tremelimumab + azacitidine | Experimental | Drug: VIDAZA, Biological: tremelimumabEvaluate MEDI4736 in combination with tremelimumab and azacitidine |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEDI4736 Evaluate MEDI4736 in MDSAlso: durvalumabMEDI4736 will be administered by IV infusion | Biological | MEDI4736 Evaluate MEDI4736 in MDS |
| VIDAZAAlso: azacitidineVIDAZA will be administered subcutaneously as described on the package insert VIDAZA will be administered in combination with MEDI4736 upon progression from MEDI4736 monotherapy | Drug | MEDI4736 + tremelimumab + azacitidine, MEDI4736 Evaluate MEDI4736 in MDS |
| tremelimumabtremelimumab will be administered by IV infusion | Biological | MEDI4736 + tremelimumab, MEDI4736 + tremelimumab + azacitidine |
Primary outcome
Subject's safety where no more than one out of six subjects experience DLTs at a given dose
Time frame: 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)
Time frame: 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.
12 secondary outcomes
Clinical outcome in terms of response: duration of response
Time frame: 2 years
Clinical outcome in terms of response: transfusion requirements
Time frame: 2 years
Clinical outcome in terms of response: progression-free survival (PFS)
Time frame: 2 years
Clinical outcome in terms of response: survival (OS)
Time frame: 2 years
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: peak concentration
Time frame: 1 year
Pharmacokinetics: MEDI4736 and tremelimumab concentrations in serum: area under the concentration-time curve
Time frame: 1 year
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: clearance
Time frame: 1 year
Pharmacokinetics: MEDI4736 and tremelimumab concentration in serum: terminal half-life
Time frame: 1 year
Immunogenicity
Time frame: 1 year
Health-related quality of life (QOL): disease- and treatment-related symptoms (Part 1 only)
Time frame: 2 years
Health-related quality of life (QOL): pain (Part 1 only)
Time frame: 2 years
Health-related quality of life (QOL): health status (Part 1 only)
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MedImmune LLC study director
MedImmune LLC
21 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MEDI4736 Evaluate MEDI4736 in MDS, VIDAZA and tremelimumab in people with Myelodysplastic Syndrome, run by MedImmune LLC at 21 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, United Kingdom, France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subject's safety where no more than one out of six subjects experience DLTs at a given dose (time frame: 180 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2019.