Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02767934
Recruitment Status : Recruiting
First Posted : May 11, 2016
Last Update Posted : May 13, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

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.

Condition or disease Intervention/treatment Phase
B Acute Lymphoblastic Leukemia Minimal Residual Disease Recurrent Acute Lymphoblastic Leukemia T Acute Lymphoblastic Leukemia Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 13, 2017
Estimated Primary Completion Date : January 1, 2021
Estimated Study Completion Date : April 1, 2021


Arm Intervention/treatment
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 2 years ]
    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.

  2. Overall Survival [ Time Frame: Up to 2 years ]
  3. Relapse-Free Survival [ Time Frame: Up to 2 years ]

Other Outcome Measures:
  1. Changes in circulating peripheral blood mononuclear cells [ Time Frame: From baseline (at screening) to end of treatment ]
    Using a flow cytometry platform, relative proportions of circulating T-cell subsets and other components of cellular immunity can be quantified and compared pre- and post-treatment with pembrolizumab.

  2. Changes in circulating serum cytokines [ Time Frame: From baseline (at screening) to end of treatment ]
    Using a flow cytometry platform, relative proportions of circulating T-cell subsets and other components of cellular immunity can be quantified and compared pre- and post-treatment with pembrolizumab.

  3. Use of next-generation sequencing-based platform as a method of minimal residual disease detection [ Time Frame: From baseline (at screening) to end of treatment ]
    Compare disease assessments using next-generation sequencing to assessments using multiparameter flow cytometry and polymerase chain reaction.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02767934


Locations
Layout table for location information
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Ryan D. Cassaday    206-606-1202    cassaday@uw.edu   
Principal Investigator: Ryan D. Cassaday         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Ryan Cassaday Fred Hutch/University of Washington Cancer Consortium

Layout table for additonal information
Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT02767934     History of Changes
Other Study ID Numbers: 9458
NCI-2016-00602 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9458 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
RG1016006 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
First Posted: May 11, 2016    Key Record Dates
Last Update Posted: May 13, 2019
Last Verified: May 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasm, Residual
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents