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Acute Myeloid LeukemiaPhase 1NCT03969446

Pembrolizumab and Decitabine With or Without Venetoclax in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome That Is Newly-Diagnosed, Recurrent, or Refractory

A Phase 1 study testing Decitabine, Pembrolizumab and Venetoclax in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by City of Hope Medical Center at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

This phase Ib trial studies the side effects and best dose of pembrolizumab and how well it works in combination with decitabine with or without venetoclax in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly-diagnosed, has come back (recurrent), or does not respond to treatment… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Decitabine, Pembrolizumab and Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteUnited States
Study dates
19 May 2020to 4 Jul 2027
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 =< 1
  • Histologically confirmed AML (not including acute promyelocytic leukemia) or MDS
  • Patients with the following diagnoses
  • Refractory/relapsed AML by World Health Organization (WHO) classification, who are not candidates for allogeneic stem cell transplantation or potentially curative chemotherapy (Extramedullary disease is allowed).
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  • MDS by WHO Classification who have failed to respond or relapsed after previous therapies
  • Must have a life expectancy of >= 3 months
  • Fully recovered (=< grade 1) from the acute toxic effects (except alopecia) or complications of prior anti-cancer therapy, including surgery
  • 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
  • White blood cells (WBC) =< 25 x 10^9/L prior to initiation of venetoclax. Cytoreduction with hydroxyurea prior to treatment and/or during cycles 1 and/or 2 may be required
  • Total bilirubin =< 2 x upper limit of normal (ULN) (unless has Gilbert's disease)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine clearance of > 30 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%
  • Pulmonary function tests diffusion capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) > 50% predicted
  • Corrected QT (QTc) =< 480 ms, Note: electrocardiogram (ECG) (single-read) 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), and active hepatitis B virus (HBV) (surface antigen negative)
  • 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

Who cannot join

  • Previous allogeneic cell transplantation
  • Previous treatment with pembrolizumab
  • Previously refractory to treatment with decitabine + venetoclax (i.e. progressed through therapy without first attaining at least a partial response)
  • Systemic steroid therapy or any other form of immunosuppressive medication
  • Received a live-virus or live-attenuated virus vaccination within 30 days of planned treatment start. Administration of killed vaccines is allowed
  • 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
Show all 30Show fewer
  • 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, antineoplastic, biological or chemotherapeutic agents during the study treatment period, or within 4 weeks or five half-lives, whichever is shorter, prior to day 1 of protocol therapy with the following exception:
  • Hydroxyurea is allowed prior to treatment with venetoclax and through cycle 2 for control of rapidly progressing leukemia
  • Strong or moderate CYP3A4 inducers within 14 days prior to day 1 of venetoclax
  • Grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit consumed within 3 days prior to the first dose of venetoclax
  • Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=<2 weeks of radiotherapy) to non-central nervous system (CNS) disease
  • Concurrent use of corticosteroids (exception: nasal or topical corticosteroids or physiologic levels for steroid replacement are allowed)
  • Granulocyte-macrophage colony-stimulating factor (GMCSF) or granulocyte colony stimulating factor (GCSF) 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
  • The following cardiac conditions:
  • Unstable angina
  • Congestive heart failure (New York Heart Association [NYHA] class III or IV; or class II with a recent decompensation requiring hospitalization or referral to a heart failure clinic within 6 months before screening)
  • Acute coronary syndrome and/or revascularization (e.g., coronary artery bypass graft, stent) within 6 months of first dose of study drug Note: Allowed heart conditions are restricted to stable angina, arrhythmia or atrial fibrillation controlled by medication, history of controlled coronary artery disease > 6 months prior to screening and medically managed
  • Pulmonary dysfunction, such as history of non-infectious pneumonitis that required steroids or current pneumonitis or idiopathic pulmonary fibrosis. Note: Allowed pulmonary conditions are restricted to mild chronic obstructive pulmonary disease (COPD), controlled asthma, resolved bacterial or fungal pneumonia, or previous pulmonary embolism (PE) that has been compensated
  • 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
  • Known history of active TB (Bacillus tuberculosis)
  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Phase 1b Study of Pembrolizumab, Decitabine +/- Venetoclax Combination Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

This phase Ib trial studies the side effects and best dose of pembrolizumab and how well it works in combination with decitabine with or without venetoclax in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly-diagnosed, has come back (recurrent), or does not respond to treatment (refractory). 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. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. This trial may help doctors find the best dose of pembrolizumab that can be safely given in combination with decitabine with or without venetoclax, and to determine what side effects are seen with this treatment.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Assess the safety and tolerability of pembrolizumab combined with decitabine, with or without the addition of venetoclax (treatment cohorts 1 and 2), by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (ACUTE MYELOID LEUKEMIA [AML] ARM) II. Assess the safety and tolerability of pembrolizumab combined with decitabine, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (MYELODYSPLASTIC SYNDROME [MDS] ARM) III. Determine the maximum tolerated dose(s)/schedule (MTD) and recommended phase 2 dose(s)/ schedule (RP2D) within each treatment arm/cohort.

III. Obtain preliminary estimates of complete remission (CR/CR with incomplete hematologic recovery [CRi]) rate(s) within each treatment arm/cohort.

SECONDARY OBJECTIVES:

  1. Obtain estimates of remission duration and survival probabilities (overall and progression-free) at 2 years.

II. Explore the possible association between pre-treatment PD-1, PD-L1, and PD-L2 and clinical response.

III. Evaluate change in PD-1, PD-L1, PD-L2 levels as a result of the combination therapy.

IV. Explore the possible association between specific T cell subsets (e.g. CD4 T regulatory cells, T naive, effector and memory cells), other immunological correlatives (e.g. T-cell receptor [TCR] repertoire analysis) including post-treatment changes, and clinical response to combination therapy.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients with AML are assigned to 1 of 2 cohorts.

COHORT I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on days 1 and 22 and decitabine IV over 1 hour on days 1-10. Patients who achieve a CR receive decitabine on days 1-5. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients with pembrolizumab IV over 30 minutes on days 1 and 22 and decitabine IV over 1 hour on days 1-10 or 1-5. Patients who achieve a CR receive decitabine on days 1-5. Patients also receive venetoclax orally (PO) once daily (QD) on days 1-14. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity.

ARM II: Patients with MDS receive pembrolizumab IV over 30 minutes on days 1 and 22 and decitabine over 1 hour on days 1-5. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients who have discontinued therapy and have not progressed are followed up at 6, 12, and 24 months post-start of treatment. Patients who progress during treatment are followed up every 3 months for 2 years.

Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DecitabineDrug

    Also called 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine

    Given IV

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

Study groups in NCT03969446
Study groupRoleWhat they receive
Cohort I Arm I (pembrolizumab, decitabine)ExperimentalPatients receive pembrolizumab IV over 30 minutes on days 1 and 22 and decitabine IV over 1 hour on days 1-10. Patients who achieve a CR receive decitabine on days 1-5. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Decitabine; Biological: Pembrolizumab
Cohort I Arm II (pembrolizumab, decitabine, venetoclax)ExperimentalPatients with pembrolizumab IV over 30 minutes on days 1 and 22 and decitabine IV over 1 hour on days 1-10 or 1-5. Patients who achieve a CR receive decitabine on days 1-5. Patients also receive venetoclax PO QD on days 1-14. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Decitabine; Biological: Pembrolizumab; Drug: Venetoclax
Cohort II (pembrolizumab, decitabine)ExperimentalPatients with MDS receive pembrolizumab IV over 30 minutes on days 1 and 22 and decitabine over 1 hour on days 1-5. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Decitabine; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

    Measured: Up to 2 years

  2. Maximum-tolerated dose (MTD)

    Will be based on the assessment of dose-limiting toxicities (DLTs) during cycle 1 and NCI CTCAE version 5.0. Standard 3+3 design rules will govern enrollment and dose de-escalation. In each arm, the dose level that produces =< 1/6 DLTs will be declared the MTD.

    Measured: Up to day 42

  3. Response to treatment

    Will obtain preliminary estimates of complete remission (CR)+CR with incomplete hematologic recovery (CRi). Patients will have their response classified according to modified Cheson, 2006 criteria (myelodysplastic syndrome cohort) and Dohner et al., 2017 criteria (acute myeloid leukemia cohort). Rates and 95% Clopper-Pearson binomial confidence interval will be calculated for the complete remission rate (patients that have confirmed CR/CRi). Response rates will also be explored based on number/type of prior therapy(ies).

    Measured: Up to 2 years

Secondary outcomes (3)

  1. Response duration

    Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: From date of first documented response (CR + CRi) to documented disease relapse or death whichever occurs first, assessed up to 2 years

  2. Overall survival

    Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: From date of first dose of study drug to date of death from any cause, assessed up to 2 years

  3. Progression-free survival

    Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: From date of first dose of study drug to first documented disease relapse/progression or death from any cause, whichever occurs first, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2019
  2. Study start19 May 2020
  3. Primary completion4 Jul 2027 (estimated)
  4. Study completion4 Jul 2027 (estimated)

Why it stopped: Accrual goal Met

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
54 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03969446
Sponsor's protocol ID
19107
Other IDs
NCI-2019-03153, 19107, P30CA033572
Status last verified
Oct 2026
First submitted
28 May 2019
Last updated
20 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Decitabine, Pembrolizumab and Venetoclax in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: paused, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03969446.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.

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