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Adoptive T Cell Therapy With DC/AML Fusion Vaccine Plus Decitabine and Venetoclax in AML

ConditionsAcute Myeloid LeukemiaAcute Myeloid Leukemia, in Relapse
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorDavid Avigan

About this trial

The goal of this research study is to test if the combination of a new T cell therapy (dendritic cell (DC) / acute myeloid leukemia (AML) primed T cells), vaccine (DC/AML fusion vaccine) and standard of care decitabine and venetoclax is feasible and safe and effective for treatment of acute myeloid leukemia (AML).

The names of the study drugs involved in this study are:

* DC/AML fusion vaccine (immune cell vaccine) * Granulocyte-macrophage colony-stimulating factor (GM-CSF) (a type of growth factor or hormone) * DC/AML Primed T cells (immune cells) * Decitabine (a type of chemotherapy drug) * Venetoclax (a type of antineoplastic agent)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must have AML at initial diagnosis for which decitabine/venetoclax is planned as standard of care therapy. This can include patients with IDH or FLT-3 mutations for whom the addition of targeted therapy agents directed at IDH or FLT-3 mutations to the decitabine/venetoclax regimen is preferred per the treating physician.

Patients with AML in first relapse after cytotoxic and/or targeted therapy for which decitabine and venetoclax therapy is appropriate standard of care. This can include patients with IDH or FLT-3 mutations for whom the addition of targeted therapy agents directed at IDH or FLT-3 mutations to the decitabine/venetoclax regimen is preferred per the treating physician.

ECOG performance status ≤ 2 (Appendix A)

total bilirubin≤ 2.0 mg/dL

Disqualifiers

Patients diagnosed with acute promyelocytic leukemia

Patients treated at initial diagnosis who are appropriate for intensive induction therapy.

Patients with active systemic autoimmune disease requiring ongoing systemic therapy are excluded. The following is an exception to this criterion: subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. Patients with paraneoplastic auto-immune manifestations related to AML are allowed.

Patients who have received a prior allogeneic transplant will be excluded.

Trial design

Design model

Sequential

Treatments tested in this trial

  • DC/AML Fusion Vaccine

    Biological/Vaccine

    Autologous fusion vaccine of dendritic cells and AML cells, via subcutaneous injection (under the skin) per standard of care.

  • T-Cell Therapy

    Biological/Vaccine

    Autologous adoptive T cells, via intravenous (into the vein) infusion, per protocol.

  • Decitabine

    Drug

    A pyrimidine nucleoside analogue, via intravenous infusion, per standard of care.

  • Venetoclax

    Drug

    A BCL-2 inhibitor, taken orally per standard of care.

  • GM-CSF

    Drug

    A Granulocyte-Macrophage Colony-Stimulating Factor, via subcutaneous injection, per standard of care.

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: Adoptive T cell therapy with DC/AML fusion vaccine, decitabine, and venetoclaxExperimental treatment 2 interventions
Group B: Dose-EscalationExperimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Successful Manufacture and Administration Rate of Vaccine-Educated T Cells

Successful manufacture and administration rate is defined as the proportion of enrolled participants for whom autologous vaccine-educated T cells are successfully manufactured and administered per protocol.

Time frame
28 weeks
2

Maximum Tolerated Dose (MTD) of Vaccine-Educated T Cells

The MTD is defined as the highest dose level that one or fewer participants experiences a dose-limiting toxicity (DLT) or one dose level below the maximum administered dose level where two or more participants experience a DLT.

Time frame
56 Days
3

Toxicity Rate of Vaccine-Educated T Cells, Including CRS, Neurotoxicity, and Infections

Toxicity rate of vaccine-educated T cells is defined as the proportion of participants who experience at least one toxicity, including cytokine release syndrome, neurotoxicity, or infections, out of all participants who receive at least one T-cell infusion.

Time frame
5 years

Secondary outcomes

1

Relapse-Free Survival (RFS) at 1 Year Post Administration of Vaccine Educated T Cells

RFS based on Kaplan-Meier method is defined as the time from the first T-cell infusion to the first documented disease relapse or death from any cause. Participants without relapse will be censored at the last disease assessment. Relapse is defined as the reappearance of blasts in the blood, or a bone marrow aspirate and biopsy showing \>5% blasts, not attributable to another cause. If there are no circulating blasts, a repeat bone marrow performed \>1 week later documenting more than 5% blasts is necessary to meet criteria for relapse.

Time frame
1 year
2

Relapse-Free Survival (RFS) at 2 Years Post Administration of Vaccine Educated T Cells

RFS based on Kaplan-Meier method is defined as the time from the first T-cell infusion to the first documented disease relapse or death from any cause. Participants without relapse will be censored at the last disease assessment. Relapse is defined as the reappearance of blasts in the blood, or a bone marrow aspirate and biopsy showing \>5% blasts, not attributable to another cause. If there are no circulating blasts, a repeat bone marrow performed \>1 week later documenting more than 5% blasts is necessary to meet criteria for relapse.

Time frame
2 years
3

MRD Negative Conversion Rate

MRD negative conversion rate is defined as the proportion of participants who convert from MRD-positive status at baseline to MRD-negative status at a subsequent post-baseline assessment,

Time frame
MRD samples are collected up to 6 months after the last cell therapy dose.
4

Median Overall Survival (OS)

Overall survival (OS), estimated using the Kaplan-Meier method, is defined as the time from registration to death from any cause. Participants without a death event will be censored at the last date they are known to be alive.

Time frame
5 years

Other outcomes

Sponsors and contacts

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

David Avigan

Lead sponsor

Beth Israel Deaconess Medical Center

Sponsor institution

Source ClinicalTrials.gov
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