Pembrolizumab and Decitabine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome That Is Newly-Diagnosed, Recurrent, or Refractory

• Status: Recruiting
• Trial end date: 2023-06-21
• Target enrollment: 0
• Participant gender: All

Summary

This phase Ib trial studies the side effects and best dose of pembrolizumab and how well it works in combination with decitabine in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly-diagnosed, has come back, or does not respond to treatment. 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. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find the best dose of pembrolizumab that can be safely given in combination with decitabine, and to determine what side effects are seen with this treatment.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Decitabine; Pembrolizumab

Criteria

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative

• Agreement to allow the use of archival blood samples and marrow from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Eastern Cooperative Oncology Group (ECOG) status of 0-1

• Histologically confirmed AML or MDS with the following characteristics

• Patients diagnosed with AML by World Health Organization (WHO) classification, meeting one of following criteria:

• Age 60 or older, newly diagnosed, untreated, who are unwilling to undergo or not candidates for conventional induction chemotherapy with cytarabine/anthracyclines

• Age 60 or older with relapsed or refractory disease

• Adult patients < 60 with previously untreated high-risk disease (complex karyotype, inv(3) or t(3;3), t(6;9), monosomal karyotype, therapy-related and secondary disease) that are unwilling to undergo or not candidates for conventional induction chemotherapy with cytarabine/anthracyclines and/or allogeneic stem cell transplantation

• Adult patients < 60 with refractory/relapsed AML who are otherwise not candidates for allogeneic stem cell transplantation

• Patients with extramedullary disease who meet one of the above criteria may be included

• Patients with a diagnosis of MDS as per WHO Classification that meets one of the following treatment history criteria

• Newly diagnosed high-risk MDS (International Prognostic Scoring System [IPSS]:

intermediate 2 and high risk)

• Refractory to or relapsed after previous therapies

• Human leukocyte antigen (HLA)-DR15-positive MDS that has failed immunosuppressive therapies

• Must have a life expectancy of >= 3 months

• Fully recovered (=< grade 1) from the acute toxic effects (except alopecia) of prior anti-cancer therapy

• Cannot be a candidate for allogeneic hematopoietic cell transplantation (alloHCT) within 90 days of starting treatment on the protocol and should be off pembrolizumab for at least 30 days to become eligible for alloHCT post-protocol therapy

• Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless has Gilbert?s disease)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN or =< 5 x ULN

• Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula

• International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN

• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN

• Left ventricular ejection fraction (LVEF) >= 50%

• Corrected QT (QTc) =< 480 ms, Note: electrocardiogram (ECG) to be performed within 14 days prior to day 1 of protocol therapy

• Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR]) (within 28 days prior to day 1 of protocol therapy)

• If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed

• Meets other institutional and federal requirements for infectious disease titer requirements

• Note: Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

• Agreement by males and females of childbearing potential to use an effective birth control method of low user dependency or abstain from heterosexual activity from 4 weeks prior to first dose of treatment throughout the study treatment period and 3 (males) to 4 (females) months from the last dose of treatment

• Childbearing potential is defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

• Also, male subjects should refrain from sperm donation from the start of treatment throughout the study treatment period and for 6 months following the last dose of treatment

Exclusion Criteria:

• Previous allogeneic cell transplantation for at least 1 year (yr) prior, have no history of graft versus host disease (GVHD) and been off all immunosuppression for at least 3 months

• Previous treatment with pembrolizumab

• Systemic steroid therapy or any other form of immunosuppressive medication

• Received a live-virus vaccination within 30 days of planned treatment start

• Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD ligand-1 (PD-L1) or PD ligand-2 (PD-L2) agent or an antibody targeting other immuno-regulatory receptors or mechanisms

• Prior therapy with an anti-CD137, anti-CTLA-4 antibody (including ipilimumab), denosumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

• Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period, or within 4 weeks prior to day 1 of protocol therapy

• Systemic cytotoxic chemotherapy, antineoplastic biologic therapy, or major surgery within 4 weeks prior to day 1 of protocol therapy

• Concurrent use of corticosteroids (exception: nasal or topical corticosteroids or physiologic levels for steroid replacement are allowed)

• Concurrent use of granulocyte-macrophage colony-stimulating factor (GMCSF) or granulocyte colony stimulating factor (GCSF), or within 7 days prior to start of study treatment

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent

• Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)

• Active central nervous system (CNS) disease

• History of (non-infectious) pneumonitis that required steroids or has current pneumonitis

• Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapies for hormone deficiencies are allowed)

• Uncontrolled active infection requiring therapy

• Seronegative for HIV Ag/Ab combo, HCV, active HBV (surface antigen negative), and syphilis (RPR).

• If positive, hepatitis C RNA quantitation must be performed

• Known history of active TB (Bacillus tuberculosis)

• History of deep venous thrombosis (DVT) or pulmonary embolism

• Symptomatic ascites or pleural effusion

• Clinically significant uncontrolled illness

• Females only: Pregnant or breastfeeding

• Any other condition that would, in the investigator?s judgment, contraindicate the patient?s participation in the clinical study due to safety concerns with clinical study procedures

• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)