Clinical Trials /

Pembrolizumab in Treating Minimal Residual Disease in Patients With Acute Lymphoblastic Leukemia

NCT02767934

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Treating Minimal Residual Disease in Patients With Acute Lymphoblastic Leukemia
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 9458
  • SECONDARY ID: NCI-2016-00602
  • SECONDARY ID: 9458
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: RG1016006
  • NCT ID: NCT02767934

Conditions

  • B Acute Lymphoblastic Leukemia
  • Minimal Residual Disease
  • Recurrent Acute Lymphoblastic Leukemia
  • T Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients 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.
  • Pembrolizumab

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

          -  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/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)

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment

          -  Has known history of, or any evidence of active, non-infectious pneumonitis

          -  Has previously received an allogeneic hematopoietic cell transplant, unless the
             following criteria are met:

               -  Detection of MRD occurred >= 21 days from stem cell infusion

               -  No active GVHD

               -  Receiving systemic steroid therapy of =< 10 mg of prednisone daily (or
                  equivalent)

               -  Has discontinued systemic immunosuppressant therapy >= 7 days prior to first dose
                  of pembrolizumab

          -  Has previously received other forms of cellular immunotherapy (e.g., chimeric antigen
             receptor-modified [CAR] T cells), unless the following criteria are met:

               -  Detection of MRD occurred >= 21 days from cell infusion

               -  Any specific manifestations of cytokine release syndrome or neurologic toxicity
                  attributable to the cellular therapy have completely resolved (i.e., < grade 1)

          -  Has an active infection requiring systemic therapy; antimicrobial prophylaxis will be
             permitted at the discretion of the treating investigator

          -  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, starting from the time of consent through 120 days
             after the last dose of trial treatment

          -  Has received prior therapy with any immune checkpoint inhibitor

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Has known active hepatitis B (e.g., hepatitis B virus surface protein antigen [HBsAg]
             reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA]
             [qualitative] is detected)

          -  Has received a live vaccine within 30 days of planned start of study therapy * Note:
             seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live
             attenuated vaccines, and are not allowed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of complete minimal residual disease response
Time Frame:Up to 2 years
Safety Issue:
Description:Will be defined as percentage of evaluable subjects who achieve a complete response. Will be evaluated with a Simon two-stage optimum design.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 2 years
Safety Issue:
Description:Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicities will be characterized in terms regarding seriousness, causality, toxicity grading, and action taken with regard to trial treatment.
Measure:Overall Survival
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Relapse-Free Survival
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:University of Washington

Last Updated

January 9, 2020