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

ConditionsAcute Myeloid LeukemiaMyelodysplastic SyndromeRecurrent Acute Myeloid LeukemiaRecurrent Myelodysplastic SyndromeRefractory Acute Myeloid LeukemiaRefractory Myelodysplastic Syndrome
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorCity of Hope Medical Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Decitabine

    Drug

    Given IV

  • Pembrolizumab

    Biological/Vaccine

    Given IV

  • Venetoclax

    Drug

    Given PO

Treatment groups

54 Participants
are divided into 3 treatment groups
Group A: Cohort I Arm I (pembrolizumab, decitabine)Experimental treatment 2 interventions
Group B: Cohort I Arm II (pembrolizumab, decitabine, venetoclax)Experimental treatment 3 interventions
Group C: Cohort II (pembrolizumab, decitabine)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

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.

Time frame
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.

Time frame
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).

Time frame
Up to 2 years

Secondary outcomes

1

Response duration

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

Time frame
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.

Time frame
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.

Time frame
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

Other outcomes

1

Change in PD-1, PD-L1, and PD-L2 levels

Time frame
Baseline up to 2 years
2

Change in T cell subset distribution

Time frame
Baseline up to 2 years
3

Change in T cell receptor repertoire

Time frame
Baseline up to 2 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

City of Hope Medical Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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