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Hypomethylation Agent

Pembrolizumab + Decitabine with or without Venetoclax for Acute Myeloid Leukemia or Myelodysplastic Syndrome

Phase 1

Recruiting

Led By Guido Marcucci

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

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).

Must not have

Strong or moderate CYP3A4 inducers within 14 days prior to day 1 of venetoclax

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial is testing the combination of the immunotherapy drug pembrolizumab with the drugs decitabine and venetoclax, to see if it is safe and effective in treating patients with newly-diagnosed, recurrent, or refractory acute myeloid leukemia or myelodysplastic syndrome.

Who is the study for?

This trial is for adults with newly-diagnosed, recurrent, or treatment-resistant acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Participants must be in good physical condition (ECOG status <=1), have a life expectancy of at least 3 months, and cannot be candidates for stem cell transplantation within the next 90 days. They should not have had certain previous treatments that were unsuccessful and must agree to use effective contraception.

What is being tested?

The trial is testing the safety and optimal dosage of pembrolizumab combined with decitabine, with or without venetoclax. Pembrolizumab is an immunotherapy drug; decitabine helps produce normal blood cells by affecting DNA; venetoclax targets proteins essential for cancer cell survival. The goal is to see how well these drugs work together against AML/MDS.

What are the potential side effects?

Possible side effects include immune system reactions leading to inflammation in various organs, infusion-related reactions from the antibodies used in treatment, fatigue, digestive issues like nausea or constipation, low blood counts increasing infection risk, liver function changes and potential heart rhythm abnormalities.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am capable of becoming pregnant or fathering a child.

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My AML has returned or didn't respond to treatment, and I can't have a stem cell transplant or curative chemo.

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My condition is confirmed as AML or MDS, not including a specific subtype.

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I am fully active and can carry on all pre-disease activities without restriction.

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I will not donate sperm during and for 6 months after treatment.

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My MDS has not improved or has returned after treatment.

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I am a woman who can have children and my pregnancy test is negative.

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I have recovered from side effects of cancer treatment, except for hair loss.

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My kidneys are functioning well enough to clear creatinine.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't taken strong or moderate CYP3A4 inducers in the last 14 days.

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I have not been treated with drugs targeting PD-1, PD-L1, PD-L2, or similar.

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I have fluid buildup in my abdomen or around my lungs causing symptoms.

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I have previously received treatments targeting the immune system.

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I have an active tuberculosis infection.

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I have an active brain or spinal cord disease.

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My condition worsened despite treatment with decitabine and venetoclax.

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I am not pregnant or breastfeeding.

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I do not have any uncontrolled serious illnesses.

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I am currently fighting an infection that needs treatment.

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I have unstable chest pain.

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I have severe heart failure or my moderate heart failure has recently worsened.

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I have had a stem cell transplant from a donor.

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I am not on steroids or any immunosuppressive medications.

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I have been treated with pembrolizumab before.

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I have not received a live-virus vaccine within the last 30 days.

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I have mild COPD, controlled asthma, or had pneumonia/PE that's now resolved.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events

Maximum-tolerated dose (MTD)

Response to treatment

Secondary study objectives

Overall survival

Progression-free survival

Response duration

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Cohort II (pembrolizumab, decitabine)Experimental Treatment2 Interventions

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.

Group II: Cohort I Arm II (pembrolizumab, decitabine, venetoclax)Experimental Treatment3 Interventions

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 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.

Group III: Cohort I Arm I (pembrolizumab, decitabine)Experimental Treatment2 Interventions

Patients 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Venetoclax

FDA approved

Decitabine

2004

Completed Phase 3

~1720

Pembrolizumab

2017