A Phase II Study of Anti-PD-1 Antibody (MK-3475; Pembrolizumab) for the Treatment of Minimal Residual Disease in Adults With Acute Lymphoblastic Leukemia
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- B Acute Lymphoblastic Leukemia
- Sponsor
- University of Washington
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Rate of Complete Minimal Residual Disease Response
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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/exclusion criteria are met
- •Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention (i.e., =\< grade 1 or at baseline) 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) leukemia and/or leukemic meningitis; subjects with previously treated CNS leukemia may participate provided they are stable (e.g., without evidence of active disease by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline) and have no evidence of leukemic blasts on analysis of cerebrospinal fluid (CSF)
Outcomes
Primary Outcomes
Rate of Complete Minimal Residual Disease Response
Time Frame: 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 Outcomes
- Overall Survival(Up to 2 years)
- Relapse-Free Survival(Up to 2 years)