Diffuse Large B-Cell LymphomaPhase 1NCT02549651
MEDI4736 Alone and in Combination With Tremelimumab or AZD9150 in Adult Subjects With Relapsed/Refractory DLBCL (D4190C00023)
A Phase 1 study testing MEDI4736, tremelimumab and AZD9150 in people with Diffuse Large B-Cell Lymphoma, run by MedImmune LLC at 13 sites in 4 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of MEDI4736 (durvalumab) alone and in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory dIffuse large B-cell lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma
- What is being tested?
- MEDI4736, tremelimumab and AZD9150
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 13 sitesin 4 countries
- Study dates
- 13 Jul 2016to 4 Feb 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Subjects with histologically confirmed relapsed or refractory DLBCL who have received at least 1 prior rituximab containing chemotherapy regimen but no more than 5 prior lines of therapy
- Eastern Cooperative Group (ECOG) performance status of 0 or 1
- Measurable disease by International Working Group (IWG) response criteria for lymphoma
- Adequate organ and marrow function
Who cannot join
- Previous immune-mediated therapy
- Subjects with prior ASCT or allogenic HCT. Subjects ineligible for available curative options after failing ASCT and have met the hematologic criteria are eligible to participate in this study. Subjects with prior allogenic HCT will be excluded.
- Documented current central nervous system involvement
- 3. Active or prior documented autoimmune or inflammatory disease within 3 years, with some exceptions 4. Concurrent or prior conventional or investigational anticancer therapy, within 28 days prior to the first dose of study medication(s)
Trial locations and contacts
13 sites in 4 countries.
13 sites in 4 countries
United States8 sites
Research Site
Albuquerque, New Mexico, 87131
Research Site
Baltimore, Maryland, 21201
Research Site
Charleston, South Carolina, 29425
Research Site
Dallas, Texas, 75390
Research Site
Durham, North Carolina, 27710
Research Site
Houston, Texas, 77030
Research Site
La Jolla, California, 92093
Research Site
Milwaukee, Wisconsin, 53226
About this study
Official title: A Phase 1b Study to Evaluate the Safety and Efficacy of MEDI4736 as Monotherapy and in Combination With Tremelimumab or AZD9150 in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma.
The purpose of this study is to evaluate the safety, tolerability, and efficacy of MEDI4736 (durvalumab) alone and in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory dIffuse large B-cell lymphoma.
Read the detailed description
This is a multicenter, open-label, dose-escalation and dose-expansion study of MEDI4736 (durvalumab) as monotherapy or in combination with either tremelimumab or AZD9150. The objectives are to describe any dose-limiting toxicities, determine the maximum tolerated dose, and evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetics, and pharmacodynamics of MEDI4736 as monotherapy or in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory diffuse large B-cell lymphoma.
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- MEDI4736, tremelimumab, AZD9150
- Keywords
- DLBCL, MEDI4736, durvalumab, tremelimumab, AZD9150, anti-PD-L1, anti-CTLA-4, immunotherapy, IMTC, STAT3
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI4736Drug
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
tremelimumabDrug
Tremelimumab is an anti-CTLA4 monoclonal antibody (MAb) administered via intravenous infusion
AZD9150Drug
AZD9150 is an antisense oligonucleotide (ASO) administered via intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| MEDI4736 | Experimental | Not described Receives: Drug: MEDI4736 |
| MEDI4736 and tremelimumab | Experimental | Not described Receives: Drug: MEDI4736; Drug: tremelimumab |
| MEDI4736 and AZD9150 | Experimental | Not described Receives: Drug: MEDI4736; Drug: AZD9150 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events
Measured: Screening through 90 days after the last dose of study medication
Number of subjects experiencing dose-limiting toxicities
Changes from baseline in laboratory parameters, vital signs, and ECGs
Measured: First dose of study medications through 28 days after the administration of MEDI4736 or MEDI4736 and tremelimumab, 35 days after administration of MEDI4736 and AZD9150
Secondary outcomes (18)
Number of subjects who develop anti-drug antibodies (ADA)
Measured: Screening through 90 days after last dose of study medication
Time to Response
Measured: Screening though 3 years after the last subject receives the first dose of study medication
Duration of Response
Measured: Screening though 3 years after the last subject receives the first dose of study medication
Progression Free survival
Measured: Screening though 3 years after the last subject receives the first dose of study medication
Time to progression
Measured: Screening though 3 years after the last subject receives the first dose of study medication
Event free survival
Measured: Screening though 3 years after the last subject receives the first dose of study medication
Overall survival
Measured: Screening though 3 years after the last subject receives the first dose of study medication
MEDI4736 Maximum Plasma Concentration (Cmax)
Measured: Measured at defined study visits from time of first dose through end of treatment
Tremelimumab Maximum Plasma Concentration (Cmax)
Measured: Measured at defined study visits from time of first dose through end of treatment
AZD9150 Maximum Plasma Concentration (Cmax)
Measured: Measured at defined study visits from time of first dose through end of treatment
MEDI4736 Minimum Plasma Concentration (Cmin)
Measured: Measured at defined study visits from time of first dose through end of treatment
Tremelimumab Minimum Plasma Concentration (Cmin)
Measured: Measured at defined study visits from time of first dose through end of treatment
AZD9150 Minimum Plasma Concentration (Cmin)
Measured: Measured at defined study visits from time of first dose through end of treatment
Individual MEDI4736 Concentrations
Measured: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Individual tremelimumab Concentrations
Measured: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Individual AZD9150 Concentrations
Measured: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Change from baseline of STAT3 RNA (signal transducer and activator of transcription)
Measured: Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months)
Baseline PD-L1 protein expression within the tumor
Measured: Measured on tumor samples provided at screening
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2015 (estimated)
- Study start13 Jul 2016
- Primary completion4 Feb 2019
- Study completion4 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-Cell LymphomaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 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
- NCT02549651
- Sponsor's protocol ID
- D4190C00023
- Status last verified
- Feb 2019
- First submitted
- 27 Aug 2015
- Last updated
- 27 Feb 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 27 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study to Evaluate the Safety and Efficacy of MEDI4736 as Monotherapy and in Combination With Tremelimumab or AZD9150 in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma.
- ClinicalTrials.gov ID
- NCT02549651
- Acronym / sponsor ID
- D4190C00023
- Conditions
- Diffuse Large B-Cell Lymphoma
- Keywords
- DLBCL, MEDI4736, durvalumab, tremelimumab, AZD9150, anti-PD-L1, anti-CTLA-4, immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 13 Jul 2016 (actual)
- Primary completion
- 4 Feb 2019 (actual)
- Study completion
- 4 Feb 2019 (actual)
- First posted
- 15 Sep 2015 (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.
The purpose of this study is to evaluate the safety, tolerability, and efficacy of MEDI4736 (durvalumab) alone and in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory dIffuse large B-cell lymphoma.
Detailed description
This is a multicenter, open-label, dose-escalation and dose-expansion study of MEDI4736 (durvalumab) as monotherapy or in combination with either tremelimumab or AZD9150. The objectives are to describe any dose-limiting toxicities, determine the maximum tolerated dose, and evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetics, and pharmacodynamics of MEDI4736 as monotherapy or in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory diffuse large B-cell lymphoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MEDI4736 | Experimental | Drug: MEDI4736 |
| MEDI4736 and tremelimumab | Experimental | Drug: MEDI4736, Drug: tremelimumab |
| MEDI4736 and AZD9150 | Experimental | Drug: MEDI4736, Drug: AZD9150 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years
- Subjects with histologically confirmed relapsed or refractory DLBCL who have received at least 1 prior rituximab containing chemotherapy regimen but no more than 5 prior lines of therapy
- Eastern Cooperative Group (ECOG) performance status of 0 or 1
- Measurable disease by International Working Group (IWG) response criteria for lymphoma
- Adequate organ and marrow function
Key exclusion criteria (4 listed)
- Previous immune-mediated therapy
- Subjects with prior ASCT or allogenic HCT. Subjects ineligible for available curative options after failing ASCT and have met the hematologic criteria are eligible to participate in this study. Subjects with prior allogenic HCT will be excluded.
- Documented current central nervous system involvement
- 3. Active or prior documented autoimmune or inflammatory disease within 3 years, with some exceptions 4. Concurrent or prior conventional or investigational anticancer therapy, within 28 days prior to the first dose of study medication(s)
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 |
|---|---|---|
| MEDI4736MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion | Drug | MEDI4736, MEDI4736 and AZD9150, MEDI4736 and tremelimumab |
| tremelimumabTremelimumab is an anti-CTLA4 monoclonal antibody (MAb) administered via intravenous infusion | Drug | MEDI4736 and tremelimumab |
| AZD9150AZD9150 is an antisense oligonucleotide (ASO) administered via intravenous infusion | Drug | MEDI4736 and AZD9150 |
Primary outcome
Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events
Time frame: Screening through 90 days after the last dose of study medication
Number of subjects experiencing dose-limiting toxicities
Time frame: First dose of study medications through 28 days after the administration of MEDI4736 or MEDI4736 and tremelimumab, 35 days after administration of MEDI4736 and AZD9150
Changes from baseline in laboratory parameters, vital signs, and ECGs
18 secondary outcomes
Number of subjects who develop anti-drug antibodies (ADA)
Time frame: Screening through 90 days after last dose of study medication
Time to Response
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
Duration of Response
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
Progression Free survival
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
Time to progression
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
Event free survival
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
Overall survival
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
MEDI4736 Maximum Plasma Concentration (Cmax)
Time frame: Measured at defined study visits from time of first dose through end of treatment
Tremelimumab Maximum Plasma Concentration (Cmax)
Time frame: Measured at defined study visits from time of first dose through end of treatment
AZD9150 Maximum Plasma Concentration (Cmax)
Time frame: Measured at defined study visits from time of first dose through end of treatment
MEDI4736 Minimum Plasma Concentration (Cmin)
Time frame: Measured at defined study visits from time of first dose through end of treatment
Tremelimumab Minimum Plasma Concentration (Cmin)
Time frame: Measured at defined study visits from time of first dose through end of treatment
AZD9150 Minimum Plasma Concentration (Cmin)
Time frame: Measured at defined study visits from time of first dose through end of treatment
Individual MEDI4736 Concentrations
Time frame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Individual tremelimumab Concentrations
Time frame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Individual AZD9150 Concentrations
Time frame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Change from baseline of STAT3 RNA (signal transducer and activator of transcription)
Time frame: Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months)
Baseline PD-L1 protein expression within the tumor
Time frame: Measured on tumor samples provided at screening
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 27 Feb 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
13 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, tremelimumab and AZD9150 in people with Diffuse Large B-Cell Lymphoma, run by MedImmune LLC at 13 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 5 inclusion and 4 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 27 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, France, Ireland, United Kingdom. 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?
Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events (time frame: Screening through 90 days after the last dose of study medication). 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 27 Feb 2019.