Acute Myeloid Leukemia
Conditions
Keywords
AML
Brief summary
AML is the most common acute leukemia in adults. Most patients can undergo allogeneic stem cell transplantation as a possible cure; however, many patients are not candidates for allogeneic transplant due to age, overall health, psychosocial factors, and/or lack of available donors. Therefore, these patients are unable to receive the therapeutic benefits of the graft-versus-leukemia effect of donor immune cells. The aim of this study is to hopefully break immune tolerance to AML cells to provide better outcomes in patients with non-favorable risk AML.
Detailed description
Non-favorable risk AML patients will undergo a preparative regimen of lymphodepletion of Flu/Mel followed by autologous transplantation. Anti-PD-1 therapy of pembrolizumab will begin on Day +1 following stem cell transplantation and will be administered every 3 weeks for a total of 8 doses. According to the literature, the risk of 2-year relapse is estimated to be 60-80% in patients with non-favorable risk AML in CR-1. With this protocol, investigators hypothesize that following lymphodepleting chemotherapy and pembrolizumab, the 2-year relapse risk will decrease to less than or equal to 35%. The one-sided Wald test at 5% significance level will be used to test the hypothesis. The size of 20 patients yields the power of 90.5% assuming that the actual 2-year leukemia-free survival is 60%.
Interventions
DRUGFludarabine
DRUGMelphalan
DRUGPembrolizumab
Sponsors
Merck Sharp & Dohme LLC
Northside Hospital, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
* Non-favorable risk AML * In CR-1 or subsequent CR * Completed at least one cycle of consolidation chemotherapy * Collection of at least 2x106/kg CD34+ cells * KPS of 70% or greater
Exclusion criteria
* Received investigational agent within 4 weeks of first dose * Prior chemotherapy, radiation therapy within 2 weeks of first dose * Hypersensitivity to pembrolizumab or any of its excipients * Received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With 2-year Relapse Risk | 2 years | Hypothesis is that following lymphodepleting chemotherapy and pembrolizumab, the 2-year relapse risk will decrease to ≤35% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess Safety of Pembrolizumab by Recording the Number of Participants With Treatment-related Adverse Events | 6 months | Assess safety of pembrolizumab in patients with AML following lymphodepleting chemotherapy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lymphodepletion Plus Pembrolizumab Fludarabine & Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1.
Fludarabine
Melphalan
Pembrolizumab | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Lymphodepletion Plus Pembrolizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 64 years |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 12 / 20 |
Outcome results
Primary
Number of Patients With 2-year Relapse Risk
Hypothesis is that following lymphodepleting chemotherapy and pembrolizumab, the 2-year relapse risk will decrease to ≤35%
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lymphodepletion Plus Pembrolizumab | Number of Patients With 2-year Relapse Risk | 10 Participants |
Secondary
Assess Safety of Pembrolizumab by Recording the Number of Participants With Treatment-related Adverse Events
Assess safety of pembrolizumab in patients with AML following lymphodepleting chemotherapy
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lymphodepletion Plus Pembrolizumab | Assess Safety of Pembrolizumab by Recording the Number of Participants With Treatment-related Adverse Events | 9 Participants |