Pembrolizumab in Treating Patients with Acute Myeloid Leukemia, Myelodysplastic Syndrome, or B Cell Lymphomas after Donor Stem Cell Transplant

Status: Active

Description

This pilot phase I trial studies the side effects of pembrolizumab in treating patients with acute myeloid leukemia, myelodysplastic syndrome, or B cell lymphomas after stem cell transplant. Monoclonal antibodies, such as pembrolizumab may block cancer growth in different ways by targeting certain cells.

Eligibility Criteria

Inclusion Criteria

  • Subjects must have signed and dated an Institutional Review Board (IRB)-approved written informed consent form in accordance with regulatory and institutional guidelines; this must be obtained before the performance of any protocol-related procedures that are not part of normal subject care
  • Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study
  • Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Subjects have undergone alloSCT > 90 days prior to enrollment from a matched-related donor (MRD), matched-unrelated donor (MUD), cord blood donor, or haplo-identical and cord blood donor
  • There must be histological confirmation of relapse after alloSCT of any of the following diseases: any mature B cell lymphoma (classical Hodgkin lymphoma [cHL] or non-Hodgkin lymphoma [NHL]), acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
  • Subjects must be off of all immunosuppressive medications for a minimum of 2 weeks with the exception of physiologic doses of corticosteroids
  • Subjects with B cell lymphoma must have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with computed tomography (CT) scan; minimum measurement must be > 15 mm in the longest diameter and > 10 mm in the short axis
  • Subjects must not have had any prior investigational agents or devices within 4 weeks of beginning study drug
  • Subjects must have no prior history of veno-occlusive disease (VOD)
  • Absolute neutrophil count (ANC) >= 500 /mcL performed within 10 days of treatment initiation
  • Platelets >= 20,000 /mcL performed within 10 days of treatment initiation
  • Hemoglobin >= 8 g/dL performed within 10 days of treatment initiation (red blood cell [RBC] transfusions are OK)
  • Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =< 1.5 x upper limit of normal (ULN) or >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN performed within 10 days of treatment initiation
  • Serum total bilirubin =< 1.5 x ULN or direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 x 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 x ULN performed within 10 days of treatment initiation
  • Albumin >= 2.0 mg/dL performed within 10 days of treatment initiation
  • International Normalized Ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy, in which case, the PT/INR should be within therapeutic range for intended use, performed within 10 days of treatment initiation
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy, in which case, the partial thromboplastin time (PTT) should be within therapeutic range for intended use, performed within 10 days of treatment initiation
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy test beta human chorionic gonadotropin (beta-hCG) within 72 hours prior to receiving the first dose of study medication
  • Female subjects with childbearing potential should be willing to use 2 methods of contraception, be surgically sterile, or abstain from heterosexual activity throughout the course of the study, until 120 days after the final dose of study medication; subjects with childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year; abstinence is acceptable if this is the established and preferred contraceptive method for the subject
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study medication until 120 days after the final dose of study medicine; abstinence is acceptable if this is the established and preferred contraceptive method for the subject

Exclusion Criteria

  • Subjects must not have known central nervous system involvement by disease (parenchymal, meningeal or cerebrospinal fluid)
  • Subjects must not have a history of any positive test for hepatitis B or hepatitis C indicating active disease or previous exposure
  • Subjects must not have a history of human immunodeficiency virus (HIV) infection
  • Subjects must not be receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to the first dose of study medication; the use of physiologic doses of corticosteroids is acceptable
  • Subjects must not be concurrently receiving disease-modifying therapy in another therapeutic investigational study
  • Subjects must not have received a prior monoclonal antibody within 4 weeks prior to the first dose of study medication, and must have recovered (=< grade 1) from adverse events related to any anti-cancer agent administered > 4 weeks previous to the first dose of study medication
  • Subjects must not have received chemotherapy or targeted small molecule therapy within 4 half-lives of the specific agent(s), or radiation therapy within 2 weeks prior to the first dose of study medication, and must have recovered (=< grade 1) from adverse events related to a previously administered agent
  • Subjects must not have received a donor lymphocyte infusion (DLI) within 8 weeks prior to the first dose of study medication
  • Subjects must not have a history of severe (grade 3-4) acute graft versus host disease (GVHD), and/or current > grade 1 acute GHVD; subjects must not have a history of active chronic GVHD (whether limited or extensive stage)
  • Subjects must not have 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
  • Subjects must not have a known history of congestive heart failure, unstable angina pectoris, or cardiac arrhythmia (with the exception of chronic and rate-controlled atrial fibrillation)
  • Subjects must not have a history of other serious underlying medical or psychiatric condition that, in the opinion of the investigator, would impair the ability to receive, tolerate and or comply with the planned treatment and follow-up
  • Subjects must not have a history of a known secondary primary malignancy that is not in remission and/or that requires active therapy; exceptions include non-melanoma skin cancers and in situ cervical cancer that has undergone curative-intent local therapy
  • Subjects must not have a known active infection requiring intravenous antibiotic therapy
  • Subjects must not have a history of (non-infectious) pneumonitis that required steroid treatment, evidence of interstitial lung disease, or active, non-infectious pneumonitis; subjects must not have active, non-infectious colitis
  • Subjects must not be pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the final dose of study medication
  • Subjects must not have received a live vaccine within 30 days prior to the first dose of study medication
  • Subjects must not be or have an immediate family member (spouse, parent, legal guardian, sibling or child) who is an investigational site sponsor or staff directly involved with the trial, unless IRB approval is granted previously

Locations & Contacts

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Justin Paul Kline
Phone: 773-702-5550
Email: jkline@medicine.bsd.uchicago.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the tolerability of pembrolizumab treatment in the setting of relapsed myeloid malignancies and mature B cell lymphomas following allogeneic stem cell transplant (alloSCT).

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT, stratified by disease type.

II. To determine the duration of response (DOR) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.

III. To determine the overall survival (OS) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.

TERTIARY OBJECTIVES:

I. To determine the effect of pembrolizumab on restoring donor chimerism in patients with relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.

II. To determine the effect of pembrolizumab on the numbers and activation status of peripheral blood T cells.

III. To compare PD-L1 expression on malignant cells at initial diagnosis and at disease relapse following alloSCT.

IV. To examine the effect of pembrolizumab on the T cell receptor (TCR) repertoire in the peripheral blood, and where available, tumor environment, following alloSCT.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 35 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
University of Chicago Comprehensive Cancer Center

Principal Investigator
Justin Paul Kline

Trial IDs

Primary ID IRB16-1195
Secondary IDs NCI-2017-00738
Clinicaltrials.gov ID NCT02981914