Acute Myeloid LeukemiaPhase 2NCT02708641
A Phase II Study of Pembrolizumab as Post-Remission Treatment of Patients ≥ 60 With AML
A Phase 2 study testing pembrolizumab in people with Acute Myeloid Leukemia, run by Michael Boyiadzis at 1 site in United States.
Trial summary
This study evaluates the effect of pembrolizumab on the duration of remission in acute myeloid leukemia. Pembrolizumab is given after complete remission is obtained in those with AML at least 60 years old who are not candidates for allogeneic stem cell transplant. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Oct 2016to Dec 2020
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- be willing and able to provide written informed consent for the trial
- be ≥ 60 years of age on day of signing informed consent
- have a newly diagnosed AML based on the World Health Organization (WHO) criteria, currently in first complete remission (CR) on a bone marrow biopsy performed within 4 weeks of treatment initiation
- have received the last dose of induction or consolidation chemotherapy within 3 months of treatment initiation
- not be eligible for or willing to proceed with allogeneic stem cell transplant or for whom allogeneic stem cell transplant is not considered standard of care
- have a performance status of ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
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- demonstrate adequate organ function, with all screening labs performed within 10 days of treatment initiation
- transfusion independent (no red blood cell or platelet transfusions in the preceding 2 weeks of screening)
- negative urine and/or serum pregnancy test
- subjects of reproductive potential must agree to use acceptable birth control method
Who cannot join
- have a diagnosis of Acute Promyelocytic Leukemia (APL) as defined by the WHO
- currently participating in or has participated in a study of an investigational agent or device within 4 weeks of treatment initiation
- have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to treatment initiation
- have prior monoclonal antibody within 4 weeks prior to study Day 1 or have not recovered from adverse events due to agents administered more than 4 weeks earlier
- have prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 have not recovered from adverse events due to previously administered agent(s)
- have a known additional malignancy that is progressing or requires active treatment except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
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- have known active central nervous system (CNS) involvement
- have an active autoimmune disease requiring systemic treatment within the past 3 months
- has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- have an uncontrolled, life-threatening active infection
- have a history or current evidence of condition, therapy, or laboratory abnormality that would preclude study participation in the opinion of the treating investigator
- have known psychiatric or substance abuse disorders that would interfere with cooperation with the trial requirements
- is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
- have received prior therapy with any antibody targeting the T-cell co-stimulation or checkpoint pathways
- have a known history of HIV
- have known active Hepatitis B or Hepatitis C
- have received a live vaccine within 30 days prior to treatment initiation
Trial locations and contacts
1 site in 1 country.
United States1 site
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase II Study of Pembrolizumab as Post-Remission Treatment of Patients ≥ 60 With Acute Myeloid Leukemia (AML) Who Are Not Transplantation Candidates
This study evaluates the effect of pembrolizumab on the duration of remission in acute myeloid leukemia. Pembrolizumab is given after complete remission is obtained in those with AML at least 60 years old who are not candidates for allogeneic stem cell transplant. The primary purpose of this study is determine if the time to relapse can be extended. Additionally, the safety and tolerability of pembrolizumab will be closely monitored.
Read the detailed description
Patients >60 years old with AML often have a dismal prognosis. Even though many of these patients are able to obtain a Complete Response to treatment, relapse occurs in the vast majority of patients. Transplants may reduce relapse rates in this population, but is only feasible in a minority of patients. AML's immunosuppressive microenvironment in general and PD-1/PD-L1 upregulation in particular appears to increase the risk of relapse. Importantly, PD-1 and its ligands are particularly increased after therapy compared to initial diagnosis. As such, PD-1 inhibition with pembrolizumab offers to limit leukemic cell immune escape, thereby allowing the patient's immune system to eradicate the submicroscopic residual disease and reducing relapse rates.
Treatment for this study is 200 mg Q3W as an appropriate dose for the switch to fixed dosing is based on simulations performed using the population PK model of Pembrolizumab showing that the fixed dose of 200 mg every 3 weeks will provide exposures that 1) are optimally consistent with those obtained with the 2 mg/kg dose every 3 weeks, 2) will maintain individual patient exposures in the exposure range established in melanoma as associated with maximal efficacy response and 3) will maintain individual patients exposure in the exposure range established in melanoma that are well tolerated and safe.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- pembrolizumab
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pembrolizumabDrug
Also called Keytruda
200 mg IV given every three weeks
| Study group | Role | What they receive |
|---|---|---|
| AML patients | Experimental | pembrolizumab 200 mg given IV once every three weeks Receives: Drug: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Relapse (TTR)
Time to recurrence of AML, including only deaths related to recurrence. Relapse of AML is defined as patients reaching remission (bone marrow contains <5% blast cells, blood cell counts return to within normal limits, no signs disease) followed by a return of leukemia cells in the marrow and a decrease in normal blood cells.
Measured: Up to 24 months
Worst Grade of Adverse Events Experienced (Unrelated to Relatedness to Study Therapy)
Worst Grade of AE experienced, regardless of relatedness to study therapy, per CTCAE v5.0.
Measured: Up to 24 months
Worst Grade of Adverse Events Experienced (at Least Probably Related to Treatment)
Worst Grade of AE experienced, at least probably related to treatment, per CTCAE v5.0.
Measured: Up to 24 months
Secondary outcomes (1)
Overall Survival (OS)
The length of time from date of start of treatment that patients are still alive.
Measured: Up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2016 (estimated)
- Study start4 Oct 2016
- Primary completion11 Jun 2020
- Study completionDec 2020
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 Acute Myeloid LeukemiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Boyiadzis
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Michael Boyiadzis, University of Pittsburgh
- Investigators
- Michael Boyiadzis, MD, MHSc, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02708641
- Sponsor's protocol ID
- 15-101
- Status last verified
- Jul 2021
- First submitted
- 10 Mar 2016
- Last updated
- 10 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Pembrolizumab as Post-Remission Treatment of Patients ≥ 60 With Acute Myeloid Leukemia (AML) Who Are Not Transplantation Candidates
- ClinicalTrials.gov ID
- NCT02708641
- Acronym / sponsor ID
- 15-101
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Michael BoyiadzisUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 4 Oct 2016 (actual)
- Primary completion
- 11 Jun 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 15 Mar 2016 (estimated)
- Results
- Posted 10 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the effect of pembrolizumab on the duration of remission in acute myeloid leukemia. Pembrolizumab is given after complete remission is obtained in those with AML at least 60 years old who are not candidates for allogeneic stem cell transplant. The primary purpose of this study is determine if the time to relapse can be extended. Additionally, the safety and tolerability of pembrolizumab will be closely monitored.
Detailed description
Patients >60 years old with AML often have a dismal prognosis. Even though many of these patients are able to obtain a Complete Response to treatment, relapse occurs in the vast majority of patients. Transplants may reduce relapse rates in this population, but is only feasible in a minority of patients. AML's immunosuppressive microenvironment in general and PD-1/PD-L1 upregulation in particular appears to increase the risk of relapse. Importantly, PD-1 and its ligands are particularly increased after therapy compared to initial diagnosis. As such, PD-1 inhibition with pembrolizumab offers to limit leukemic cell immune escape, thereby allowing the patient's immune system to eradicate the submicroscopic residual disease and reducing relapse rates.
Treatment for this study is 200 mg Q3W as an appropriate dose for the switch to fixed dosing is based on simulations performed using the population PK model of Pembrolizumab showing that the fixed dose of 200 mg every 3 weeks will provide exposures that 1) are optimally consistent with those obtained with the 2 mg/kg dose every 3 weeks, 2) will maintain individual patient exposures in the exposure range established in melanoma as associated with maximal efficacy response and 3) will maintain individual patients exposure in the exposure range established in melanoma that are well tolerated and safe.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AML patients | Experimental | Drug: pembrolizumabpembrolizumab 200 mg given IV once every three weeks |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- be willing and able to provide written informed consent for the trial
- be ≥ 60 years of age on day of signing informed consent
- have a newly diagnosed AML based on the World Health Organization (WHO) criteria, currently in first complete remission (CR) on a bone marrow biopsy performed within 4 weeks of treatment initiation
- have received the last dose of induction or consolidation chemotherapy within 3 months of treatment initiation
- not be eligible for or willing to proceed with allogeneic stem cell transplant or for whom allogeneic stem cell transplant is not considered standard of care
Key exclusion criteria (17 listed)
- have a diagnosis of Acute Promyelocytic Leukemia (APL) as defined by the WHO
- currently participating in or has participated in a study of an investigational agent or device within 4 weeks of treatment initiation
- have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to treatment initiation
- have prior monoclonal antibody within 4 weeks prior to study Day 1 or have not recovered from adverse events due to agents administered more than 4 weeks earlier
- have prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 have not recovered from adverse events due to previously administered agent(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 |
|---|---|---|
| pembrolizumabAlso: Keytruda200 mg IV given every three weeks | Drug | AML patients |
Primary outcome
Time to Relapse (TTR)
Time frame: Up to 24 months
Time to recurrence of AML, including only deaths related to recurrence. Relapse of AML is defined as patients reaching remission (bone marrow contains <5% blast cells, blood cell counts return to within normal limits, no signs disease) followed by a return of leukemia cells in the marrow and a decrease in normal blood cells.
Worst Grade of Adverse Events Experienced (Unrelated to Relatedness to Study Therapy)
Time frame: Up to 24 months
Worst Grade of AE experienced, regardless of relatedness to study therapy, per CTCAE v5.0.
Worst Grade of Adverse Events Experienced (at Least Probably Related to Treatment)
Time frame: Up to 24 months
Worst Grade of AE experienced, at least probably related to treatment, per CTCAE v5.0.
1 secondary outcome
Overall Survival (OS)
Time frame: Up to 48 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Michael Boyiadzis, MD, MHSc principal investigator
UPMC Hillman 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 pembrolizumab in people with Acute Myeloid Leukemia, run by Michael Boyiadzis 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 10 inclusion and 17 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 Aug 2021. 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 10 Aug 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?
Time to Relapse (TTR) (time frame: Up to 24 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 10 Aug 2021.