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Assessing PI3K Gamma Inhibition With Azacitidine, Venetoclax and Eganelisib in Patients With Acute Myeloid Leukemia

ConditionsLeukemia, MyeloidLeukemiaAcute Myeloid LeukemiaRefractory Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-90
SponsorJacqueline Garcia, MD

About this trial

This study is to evaluate the safety and preliminary efficacy of adding the PI3K-gamma inhibitor, eganelisib, to a standard of care treatment option with combination venetoclax and azacitidine in participants with acute myeloid leukemia (AML).

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

* Venetoclax (a type of BCL-2 inhibitor) * Azacitidine (a type of Demethylating Agent) * Eganelisib (a type of PI3K-gamma inhibitor)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Group A: Relapsed or Refractory: Subjects with relapsed or refractory AML or relapsed/refractory AML, who are not recommended for any approved targeted therapy must meet any one of the following criteria: (1) morphologic relapse (at least 5% blasts), or (2) refractory to intensive chemotherapy (at least one cycle of cytarabine and anthracycline-based intensive regimen) or at least 2 cycles of prior HMA/venetoclax-based therapy (without CR/CRh/CRi). No limit to prior lines of AML therapy. OR

(Expansion only) Group B: Untreated AML with ELN 2022 adverse risk disease: Subjects with newly diagnosed or previously untreated AML must be ineligible for intensive chemotherapy based on Ferrara criteria (age ≥75 years or presence of co- morbidity).

Evidence of marrow involved AML.

Age 18-90 years. Because no dosing or adverse event data are currently available on the use of eganelisib in participants <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.

Disqualifiers

Prior systemic cancer therapy is allowed as long as >14 days prior to study treatment start. Hormonal therapy may be allowed if approved by Sponsor-Investigator.

Major surgery within 28 days prior to study treatment start.

Allogeneic stem cell transplant within 100 days prior to study treatment start.

Active graft-versus-host disease (GVHD) after allogeneic stem cell transplantation or chronic GVHD requiring systemic steroid administration. Topical therapies are allowed for controlled GVHD.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Eganelisib

    Drug

    PI3K-gamma inhibitor, capsule taken orally per protocol.

  • Azacitidine

    Drug

    Demethylating Agent, single use vial, via subcutaneous (under the skin) injection or intravenous (into the vein) infusion per standard of care.

  • Venetoclax

    Drug

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

Treatment groups

48 Participants
are divided into 2 treatment groups
Group A: Dose-Escalation EganelisibExperimental treatment 3 interventions
Group B: Dose-Expansion EganelisibExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Eganelisib Recommended Phase 2 Dose (RP2D)

The eganelisib (daily) RP2D in combination with azacitidine 75 mg/m\^2/day on days 1-7 and venetoclax 400 mg daily (28 days) is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The RP2D is based on the Bayesian optimal interval design (BOIN). The RP2D may also be based on available pharmacokinetic (PK) and pharmacodynamic (PD) data.

Time frame
1 cycle=28 days
2

Recommended Phase 2 Dose (RP2D)

Number of Participants experiencing protocol-defined DLT

Time frame
1 cycle=28 days

Secondary outcomes

1

Treatment-Related Grade 3-4 Adverse Event (AE) Rate

Percentage of participants who experience an AE of grade 3 or 4 with treatment attribution of possible, probable or definite per Common Toxicity Adverse Event Criteria (CTCAE) version 5.

Time frame
through study completion, an average of 2 years
2

Eganelisib Feasibility Rate

Percentage of participants completing \>/= 75% of planned doses of eganelisib.

Time frame
First 28 days
3

Eganelisib Area Under the Plasma Concentration versus Time Curve (AUC)

Eganelisib AUC exposure is quantified by the integral of the plasma drug concentration-time curve over a specified time interval associated with pharmacokinetic sampling.

Time frame
Up to 4 months
4

Complete Remission (CR) Rate

Percentage of participants achieving CR on treatment per established criteria for adult acute myeloid leukemia: European Leukemia Network (ELN) 2022

Time frame
Up to 4 months

Other outcomes

Sponsors and contacts

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

Jacqueline Garcia, MD

Lead sponsor

Dana-Farber Cancer Institute

Sponsor institution

Stelexis BioSciences, Inc.

Collaborator

Source ClinicalTrials.gov
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