B Acute Lymphoblastic Leukemia, Minimal Residual Disease, Recurrent Acute Lymphoblastic Leukemia, T Acute Lymphoblastic Leukemia
Conditions
Brief summary
This phase II trial studies how well pembrolizumab works in treating small amounts of cancer cells that remain after attempts to remove the cancer has been made in patients with acute lymphoblastic leukemia. 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.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the efficacy of pembrolizumab in minimal residual disease (MRD)-positive acute lymphoblastic leukemia (ALL). SECONDARY OBJECTIVES: I. To describe the toxicity profile of pembrolizumab in patients with previously-treated ALL. II. To gain a preliminary assessment of how MRD response translates into relapse-free and overall survival. EXPLORATORY OBJECTIVES: I. To compare disease assessments by multiparameter flow cytometry (MFC) and polymerase chain reaction (PCR) to a newly-developed and more sensitive next generation sequencing (NGS)-based platform. II. To correlate response to pembrolizumab to immunologic markers in peripheral blood and bone marrow specimens. III. To evaluate if treatment with pembrolizumab has a measurable impact on hematopoietic engraftment and graft-vs-host disease (GVHD) in patients who subsequently undergo allogeneic hematopoietic cell transplantation (HCT). OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving complete MRD response may receive up to 1 additional year of treatment at the discretion of the investigator. After completion of study treatment, patients are followed up every 3 months for up to 2 years.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALPembrolizumab
Given IV
Sponsors
National Cancer Institute (NCI)
University of Washington
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
* All subjects must have a diagnosis of ALL of either B-cell, T-cell, or mixed (i.e., B/T lineage) * Be willing and able to provide written informed consent for the trial * Presence of MRD (defined as \< 5% blasts in the bone marrow by morphologic assessment and no clinically-apparent extramedullary disease but with quantifiably-measurable disease as assessed by either MFC or PCR) under any of the following circumstances: * MRD persistence \>= 11 weeks after the start of initial therapy * MRD persistence \>= 2 weeks after the start of salvage therapy, or * MRD reappearance at any time * For patients with Philadelphia chromosome positive (Ph+) disease, have previously received treatment with \>= 1 Abelson (ABL) kinase inhibitor (e.g., imatinib, dasatinib, etc.) or are ineligible for such treatment * Have previously received or are ineligible for treatment with blinatumomab; ineligibility will include (but not be limited to) cluster of differentiation 19 (CD19)-negative disease, denial of insurance coverage, physician discretion, and/or patient refusal * Be willing to provide tissue from a newly obtained bone marrow aspirate and/or biopsy; newly-obtained is defined as a specimen obtained up to 28 days prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g., inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the principal investigator (PI) * Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale * Absolute neutrophil count (ANC) \>= 1,000 /mcL (performed within 10 days of treatment initiation) * Hemoglobin \>= 8 g/dL (performed within 10 days of treatment initiation) * Platelets \>= 50,000 /mcL (performed within 10 days of treatment initiation) * Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance \>= 60 mL/min/1.73 m\^2 for subject with creatinine levels \> 1.5 X institutional ULN (performed within 10 days of treatment initiation) (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) * Serum total bilirubin =\< 1.5 X ULN 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 ULN (performed within 10 days of treatment initiation) * International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation) * Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation) * Female subjects of childbearing potential should have a negative urine or serum pregnancy within 3 days 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 * 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
Exclusion criteria
* Is currently participating and receiving study therapy or has participated in a study of an investigational new drug 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 bacillus tuberculosis (TB) * Has a known 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 (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 or with hematologic toxicity that has recovered to levels above that stated in inclusion criterion are an exception to this criterion and may qualify for the study if all other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Complete Minimal Residual Disease Response | Up to 2 years | Will be defined as percentage of evaluable subjects who achieve a complete response. Will be evaluated with a Simon two-stage optimum design. |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival | Up to 2 years |
| Relapse-Free Survival | Up to 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Pembrolizumab) Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving complete MRD response may receive up to 1 additional year of treatment at the discretion of the investigator.
Laboratory Biomarker Analysis: Correlative studies
Pembrolizumab: Given IV | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Treatment (Pembrolizumab) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 52.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 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 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 12 |
| other Total, other adverse events | 6 / 12 |
| serious Total, serious adverse events | 1 / 12 |
Outcome results
Primary
Rate of Complete Minimal Residual Disease Response
Will be defined as percentage of evaluable subjects who achieve a complete response. Will be evaluated with a Simon two-stage optimum design.
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab | Rate of Complete Minimal Residual Disease Response | 1 Participants |
Secondary
Overall Survival
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Overall Survival | 12.7 months |
Secondary
Relapse-Free Survival
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab | Relapse-Free Survival | 3.1 months |