High Risk Myelodysplastic SyndromePhase 2NCT03094637
Azacitidine and Pembrolizumab in Treating Patients With Myelodysplastic Syndrome
A Phase 2 study testing Azacitidine and Pembrolizumab in people with High Risk Myelodysplastic Syndrome and IPSS Risk Category Intermediate-1, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies the side effects of azacitidine and pembrolizumab and to see how well they work in treating patients with myelodysplastic syndrome. Azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Risk Myelodysplastic Syndrome, IPSS Risk Category Intermediate-1, Myelodysplastic Syndrome
- What is being tested?
- Azacitidine and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Nov 2017to 6 Nov 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Voluntary signed informed consent before performance of any study related procedure not part of normal medical care indicating that the patient is aware of the investigation and nature of this study in keeping with institutional policies and with the understanding that the consent may be withdrawn with the subject at any time without prejudice to future medical care
- Intermediate 1 (INT-1) or higher risk MDS defined by International Prognostic Scoring System (IPSS) criteria
- Patients can or cannot have receive prior therapy with hypomethylating agent but will be allocated to specific patient cohorts based on their prior exposure. Patients that had received prior hypomethylating agent therapy should have at least received 6 cycles of therapy and not achieved any response or had progressed after any given number of cycles
- Eastern Cooperative Oncology Group (ECOG) performance of 0 to 2
- Male patients, even if surgically sterilized, should agree to practice effective barrier contraception for the entire study treatment period and through 120 days after the last dose of the study treatment or agree to completely abstain from heterosexual intercourse. Female patients who are postmenopausal for at least one year before the screening visit or are surgical sterile or if they are of child bearing potential must have a negative pregnancy test within 72 hours of treatment of the start date and agree to practice two effective methods of contraception forms at the same time from the time of signing the informed consent through 120 days of the last dose of the study treatment or agree to completely abstain from heterosexual intercourse
- Willingness and ability to comply with scheduled visits treatment plans, laboratory tests and other study procedures
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- Serum creatinine or measured or calculated creatine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrcL]) =< 2.0 x upper limit of normal (ULN) or >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (performed within 10 days of treatment initiation). Creatinine clearance should be calculated per institutional standard
- Serum total bilirubin =< 2.0 x ULN (unless considered due to Gilbert's disease or leukemia disease) or direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 10 days of treatment initiation)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (unless considered due to Gilbert's disease or leukemia disease) or =< 5 x ULN for subjects with liver metastases (performed within 10 days of treatment initiation)
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
- Patients must receive a minimum dose of azacitidine of 75mg/(m)(2) dose
Who cannot join
- Significant medical psychiatric cognitive or other conditions that may compromise the patient ability to understand the patient information to give informed consent to comply with the study protocol or to complete the study
- Any severe or concurrent disease or condition including uncontrolled systemic infection, congestive heart failure, angina pectoris or cardiac arrhythmia and autoimmune processes that in the opinion of the investigator would make the patient inappropriate for study participation
- Patients with known hypersensitivity to 5-azacitidine or MK3475 or any of their excipients
- Prior history of stem cell transplantation
- For patients in the relapse or refractory cohort, any other therapy not being a hypomethylating agent after hypomethylating agents (HMA) failure or more than 4 months since completion of last cycle of hypomethylating agent. Please note that hypomethylating agent may include second generation compounds such as SGI-110, oral decitabine or oral azacitidine and will also include combinations with investigational agents
- Treatment with other investigational agents including chemotherapy, immunotherapy, or radiation therapy within a month prior to the start of this clinical trial
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- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has a known history of active TB (Bacillus tuberculosis)
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has known history of, or any evidence of active, non-infectious pneumonitis
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of the Combination of Azacitidine and Pembrolizumab for Patients With MDS
This phase II trial studies the side effects of azacitidine and pembrolizumab and to see how well they work in treating patients with myelodysplastic syndrome. Azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving azacitidine and pembrolizumab may work better at treating myelodysplastic syndrome.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety of the combination of azacitidine and MK3475 (pembrolizumab) in patients with higher risk myelodysplastic syndrome (MDS).
II. To explore the clinical activity (response, survival effect) of the combination of azacitidine with MK-3475 in patients with higher risk MDS.
EXPLORATORY OBJECTIVES:
- To study the biological effects of the combination of azacitidine and pembrolizumab in patients with MDS treated on this study.
OUTLINE:
Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7, and pembrolizumab IV over 30 minutes every 3 weeks. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days, every 12 weeks for 1 year, then annually thereafter.
- Conditions
- High Risk Myelodysplastic Syndrome, IPSS Risk Category Intermediate-1, Myelodysplastic Syndrome
- Being tested
- Azacitidine, Pembrolizumab
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given IV
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (azacitidine, pembrolizumab) | Experimental | Patients receive azacitidine Intravenous (IV) over 10-40 minutes or Subcutaneous (SC) on days 1-7, and pembrolizumab IV over 30 minutes every 3 weeks. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: Azacitidine; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) Defined as Complete Response + Partial Response + Hematological Improvement
Will estimate the ORR for the experimental treatments, along with the 95% credible intervals. The association between ORR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Measured: Up to 2 years 4 months
Event Free Survival
Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Measured: Up to 4 years
Overall Survival
Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests. Overall Survival will be presented by median survival, which is the time point at which the cumulative survival drops below 50%. If there is no median survival (not reached), it means the cumulative survival was more than 50%.
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2017
- Study start6 Nov 2017
- Primary completion6 Nov 2021
- Study completion6 Nov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for High Risk Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Guillermo Garcia-Manero, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03094637
- Sponsor's protocol ID
- 2016-0343
- Other IDs
- NCI-2018-01238, 2016-0343
- Status last verified
- Feb 2023
- First submitted
- 20 Mar 2017
- Last updated
- 22 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- 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 22 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Combination of Azacitidine and Pembrolizumab for Patients With MDS
- ClinicalTrials.gov ID
- NCT03094637
- Acronym / sponsor ID
- 2016-0343
- Conditions
- High Risk Myelodysplastic Syndrome, IPSS Risk Category Intermediate-1, Myelodysplastic Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 6 Nov 2017 (actual)
- Primary completion
- 6 Nov 2021 (actual)
- Study completion
- 6 Nov 2023 (estimated)
- First posted
- 29 Mar 2017 (actual)
- Results
- Posted 1 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies the side effects of azacitidine and pembrolizumab and to see how well they work in treating patients with myelodysplastic syndrome. Azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving azacitidine and pembrolizumab may work better at treating myelodysplastic syndrome.
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety of the combination of azacitidine and MK3475 (pembrolizumab) in patients with higher risk myelodysplastic syndrome (MDS).
II. To explore the clinical activity (response, survival effect) of the combination of azacitidine with MK-3475 in patients with higher risk MDS.
EXPLORATORY OBJECTIVES:
- To study the biological effects of the combination of azacitidine and pembrolizumab in patients with MDS treated on this study.
OUTLINE:
Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7, and pembrolizumab IV over 30 minutes every 3 weeks. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days, every 12 weeks for 1 year, then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (azacitidine, pembrolizumab) | Experimental | Drug: Azacitidine, Biological: PembrolizumabPatients receive azacitidine Intravenous (IV) over 10-40 minutes or Subcutaneous (SC) on days 1-7, and pembrolizumab IV over 30 minutes every 3 weeks. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Voluntary signed informed consent before performance of any study related procedure not part of normal medical care indicating that the patient is aware of the investigation and nature of this study in keeping with institutional policies and with the understanding that the consent may be withdrawn with the subject at any time without prejudice to future medical care
- Intermediate 1 (INT-1) or higher risk MDS defined by International Prognostic Scoring System (IPSS) criteria
- Patients can or cannot have receive prior therapy with hypomethylating agent but will be allocated to specific patient cohorts based on their prior exposure. Patients that had received prior hypomethylating agent therapy should have at least received 6 cycles of therapy and not achieved any response or had progressed after any given number of cycles
- Eastern Cooperative Oncology Group (ECOG) performance of 0 to 2
- Male patients, even if surgically sterilized, should agree to practice effective barrier contraception for the entire study treatment period and through 120 days after the last dose of the study treatment or agree to completely abstain from heterosexual intercourse. Female patients who are postmenopausal for at least one year before the screening visit or are surgical sterile or if they are of child bearing potential must have a negative pregnancy test within 72 hours of treatment of the start date and agree to practice two effective methods of contraception forms at the same time from the time of signing the informed consent through 120 days of the last dose of the study treatment or agree to completely abstain from heterosexual intercourse
Key exclusion criteria (23 listed)
- Significant medical psychiatric cognitive or other conditions that may compromise the patient ability to understand the patient information to give informed consent to comply with the study protocol or to complete the study
- Any severe or concurrent disease or condition including uncontrolled systemic infection, congestive heart failure, angina pectoris or cardiac arrhythmia and autoimmune processes that in the opinion of the investigator would make the patient inappropriate for study participation
- Patients with known hypersensitivity to 5-azacitidine or MK3475 or any of their excipients
- Prior history of stem cell transplantation
- For patients in the relapse or refractory cohort, any other therapy not being a hypomethylating agent after hypomethylating agents (HMA) failure or more than 4 months since completion of last cycle of hypomethylating agent. Please note that hypomethylating agent may include second generation compounds such as SGI-110, oral decitabine or oral azacitidine and will also include combinations with investigational agents
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 |
|---|---|---|
| AzacitidineAlso: 5 AZC, 5-AC, 5-Azacytidine, 5-AZCGiven IV | Drug | Treatment (azacitidine, pembrolizumab) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Treatment (azacitidine, pembrolizumab) |
Primary outcome
Overall Response Rate (ORR) Defined as Complete Response + Partial Response + Hematological Improvement
Time frame: Up to 2 years 4 months
Will estimate the ORR for the experimental treatments, along with the 95% credible intervals. The association between ORR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Event Free Survival
Time frame: Up to 4 years
Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Overall Survival
Time frame: Up to 4 years
Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests. Overall Survival will be presented by median survival, which is the time point at which the cumulative survival drops below 50%. If there is no median survival (not reached), it means the cumulative survival was more than 50%.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- MD Anderson Cancer CenterLink provided by the sponsor.
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ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
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First-in-human (FIH) Trial of GEN3018 in Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) or Higher-risk Myelodysplastic Syndrome (HR-MDS)
R/R AML, R/R HR-MDS
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.
Guillermo Garcia-Manero principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azacitidine and Pembrolizumab in people with High Risk Myelodysplastic Syndrome and IPSS Risk Category Intermediate-1, run by M.D. Anderson Cancer Center at 1 site in United States.
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 13 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 22 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (ORR) Defined as Complete Response + Partial Response + Hematological Improvement (time frame: Up to 2 years 4 months). The study lists 3 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 22 Mar 2023.