Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndromes
Conditions
Brief summary
This is a single arm, open-label, Phase 1b study of pembrolizumab for patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) whose disease has relapsed after receiving allogeneic hematopoetic stem cell transplant.
Interventions
DRUGPembrolizumab
200mg IV every 21 days
Sponsors
Merck Sharp & Dohme LLC
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL) or Myelodysplastic Syndrome (MDS) in confirmed relapse * Confirmation of 'measurable disease' * Patient may not have received definitive salvage chemotherapy for their post-transplant relapse within the past 21 days. * Be willing and able to provide written informed consent/assent for the trial * Be ≥ 18 years of age on day of signing informed consent * Be willing to provide tissue from bone marrow biopsies * Have a performance status of 0, to 1 on the ECOG Performance Scale. Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death. * Demonstrate adequate organ function * 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. * Female subjects of childbearing potential must be willing to use an adequate method of contraception * Male subjects of childbearing potential must agree to use an adequate method of contraception
Exclusion criteria
* Has had relapse prior to primary neutrophil engraftment or ≤21 days post HCT. * Has received \>1 line of chemotherapy or other treatment directed towards post-transplant relapse prior to study entry * Rapidly progressive relapse requiring urgent chemotherapy as determined by treating physician * Is currently participating and receiving study therapy of an investigational agent and received study therapy within 2 weeks of the first dose of treatment. * Has a diagnosis of active GvHD (≥ Grade I) * Receiving systemic steroid therapy of \> 10mg prednisone daily or equivalent\* * Has received GM-CSF within 14 days of first dose of pembrolizumab * Has a known history of active TB (Bacillus Tuberculosis)Hypersensitivity to pembrolizumab or any of its excipients * Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered from adverse events * Has had prior chemotherapy within 21 days or radiation therapy within 14 days prior to study Day 1 or who has not recovered from adverse events * Has a known additional (secondary) malignancy that is progressing or requires active treatment * Has known or suspected active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis * 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 * 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) * Has known active Hepatitis B or Hepatitis C * Has received a live vaccine within 30 days of planned start of study therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients That Demonstrate Clinical Benefit From Treatment | Day 77 | This study will assess if the study drug is promising for further study. The study drug will be considered promising if at least 4 patients receive a clinical benefit or if any complete response is seen. Clinical benefit is defined as either stable disease, partial remission or complete remission to treatment. Complete remission (CR) will be defined as achieving a morphologic leukemia free state by achieving all of the following criteria: bone marrow myeloblasts \< 5% by morphologic assessment; AND absence of circulating blasts with phenotypic or morphologic features of leukemia (e.g. Auer rods) AND no evidence of extramedulary disease. Partial remission (PR) will be defined as a ≥ 50% reduction in bone marrow blast percentage to 5-25% or marrow blasts \< 5% with persistent Auer rods, flow cytometric or cytogenetic disease. SD will be defined as ≤ 5% increase in blasts or decreased blast percentage in the bone marrow that does not meet the criteria for PR. |
| The Number of Patients That Respond to Treatment | Day 77 | This study will assess the number of patients that respond to treatment by overall response rate (ORR). ORR is defined as the number of patients will complete remission and partial remission. Complete remission (CR) will be defined as achieving a morphologic leukemia free state by achieving all of the following criteria: bone marrow myeloblasts \< 5% by morphologic assessment; AND absence of circulating blasts with phenotypic or morphologic features of leukemia (e.g. Auer rods) AND no evidence of extramedulary disease. Partial remission (PR) will be defined as a ≥ 50% reduction in bone marrow blast percentage to 5-25% or marrow blasts \< 5% with persistent Auer rods, flow cytometric or cytogenetic disease. |
| Graft Versus Host Disease (GvHD) or Other Significant Immune Mediated Toxicities | 30 Days Post Treatment | The number of patients that experience Graft Versus Host Disease (GvHD) or other significant immune mediated toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 1 Year | The number of patients alive at 1 year |
| Event- Free Survival | 1 Year | The number of patients alive at 1 year without disease |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Pembrolizumab: 200mg IV every 21 days | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Death | 3 |
Baseline characteristics
| Characteristic | Pembrolizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 1 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 16 |
| other Total, other adverse events | 6 / 16 |
| serious Total, serious adverse events | 16 / 16 |
Outcome results
Primary
Graft Versus Host Disease (GvHD) or Other Significant Immune Mediated Toxicities
The number of patients that experience Graft Versus Host Disease (GvHD) or other significant immune mediated toxicities
Time frame: 30 Days Post Treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab | Graft Versus Host Disease (GvHD) or Other Significant Immune Mediated Toxicities | GVHD | 9 Participants |
| Pembrolizumab | Graft Versus Host Disease (GvHD) or Other Significant Immune Mediated Toxicities | mmune-related SAEs | 2 Participants |
Primary
The Number of Patients That Demonstrate Clinical Benefit From Treatment
This study will assess if the study drug is promising for further study. The study drug will be considered promising if at least 4 patients receive a clinical benefit or if any complete response is seen. Clinical benefit is defined as either stable disease, partial remission or complete remission to treatment. Complete remission (CR) will be defined as achieving a morphologic leukemia free state by achieving all of the following criteria: bone marrow myeloblasts \< 5% by morphologic assessment; AND absence of circulating blasts with phenotypic or morphologic features of leukemia (e.g. Auer rods) AND no evidence of extramedulary disease. Partial remission (PR) will be defined as a ≥ 50% reduction in bone marrow blast percentage to 5-25% or marrow blasts \< 5% with persistent Auer rods, flow cytometric or cytogenetic disease. SD will be defined as ≤ 5% increase in blasts or decreased blast percentage in the bone marrow that does not meet the criteria for PR.
Time frame: Day 77
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | The Number of Patients That Demonstrate Clinical Benefit From Treatment | 6 Participants |
Primary
The Number of Patients That Respond to Treatment
This study will assess the number of patients that respond to treatment by overall response rate (ORR). ORR is defined as the number of patients will complete remission and partial remission. Complete remission (CR) will be defined as achieving a morphologic leukemia free state by achieving all of the following criteria: bone marrow myeloblasts \< 5% by morphologic assessment; AND absence of circulating blasts with phenotypic or morphologic features of leukemia (e.g. Auer rods) AND no evidence of extramedulary disease. Partial remission (PR) will be defined as a ≥ 50% reduction in bone marrow blast percentage to 5-25% or marrow blasts \< 5% with persistent Auer rods, flow cytometric or cytogenetic disease.
Time frame: Day 77
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | The Number of Patients That Respond to Treatment | 3 Participants |
Secondary
Event- Free Survival
The number of patients alive at 1 year without disease
Time frame: 1 Year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Event- Free Survival | 31.3 percentage of participants |
Secondary
Overall Survival
The number of patients alive at 1 year
Time frame: 1 Year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab | Overall Survival | 37.5 percentage of participants |