RECRUITING

Venetoclax and HMA Treatment of Older and Unfit Adults With FLT3 Mutated Acute Myeloid Leukemia (AML) (A MyeloMATCH Treatment Trial)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase II MyeloMATCH treatment trial compares the usual treatment of azacitidine and venetoclax to the combination treatment of azacitidine, venetoclax and gilteritinib in treating older and unfit patients with acute myeloid leukemia and FLT3 mutations. Azacitidine is a drug that is absorbed into DNA and leads to the activation of cancer suppressor genes, which are genes that help control cell growth. 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. Gilteritinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply. This study may help doctors find out if these different approaches are better than the usual approaches. To decide if they are better, the study doctors are looking to see if the study drugs lead to a higher percentage of patients achieving a deeper remission compared to the usual approach.

Official Title

A Randomized Phase II Study of Venetoclax and HMA-Based Therapies for the Treatment of Older and Unfit Adults With Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia (AML): A MyeloMATCH Treatment Trial

Quick Facts

Study Start:2024-09-27

Study Completion:2025-10-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06317649

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patient must be ≥ 60 years of age or adults ˂ 60 who in the opinion of the treating physician are better served by azanucleoside-based therapy rather than intensive, cytarabine-based induction based on clinical status (i.e., performance status, age \> 75 years), organ dysfunction, or disease biology * Patient must have a morphologically confirmed diagnosis of AML according to the World Health Organization (WHO) 2016 classification excluding acute promyelocytic leukemia (APL) with PML-RARA, AML with RUNX1-RUNX1T1, or AML with CBFB-MYH11 * Patient must have no prior therapy for AML with the exception of hydroxyurea and all-trans retinoic acid (ATRA), or leukapheresis. Patients with cytarabine-based emergency therapy prior to the start of therapy on this trial are eligible * Patient must have no prior therapy with hypomethylating agents or FLT3 inhibitors * Patient must have the FLT3-ITD or D835 mutation based on MyeloMATCH Master Screening and Reassessment Protocol (MSRP) * Patient must be assigned to this protocol by the myeloMATCH MSRP * Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. * All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. * A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) * Patient of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Contraception measures must continue for 30 days after the last dose of venetoclax for all patients and for 6 months after the last dose of gilteritinib for patients of childbearing potential and for 4 months after the last dose of gilteritinib for male patients with partners of childbearing potential. Patient must not breastfeed during treatment and for 2 months after treatment ends * Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible * Total bilirubin 2X ≤ institutional upper limit of normal (ULN) (unless thought to be elevated due to disease involvement or Gilbert's syndrome) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN * Either measured or estimated by Cockcroft-Gault equation * Creatinine clearance of ≥ 30 mL/min/1.73m\^2 * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration/randomization are eligible for this trial * Patients must not have a baseline corrected QT interval ≥ 480 msec using Fredericia correction (QTcF). * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Patient must not have the medical necessity for ongoing treatment with a strong CYP3A4 inducing drug * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better * Patients must not have an active or uncontrolled infection	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

* Patient must be ≥ 60 years of age or adults ˂ 60 who in the opinion of the treating physician are better served by azanucleoside-based therapy rather than intensive, cytarabine-based induction based on clinical status (i.e., performance status, age \> 75 years), organ dysfunction, or disease biology
* Patient must have a morphologically confirmed diagnosis of AML according to the World Health Organization (WHO) 2016 classification excluding acute promyelocytic leukemia (APL) with PML-RARA, AML with RUNX1-RUNX1T1, or AML with CBFB-MYH11
* Patient must have no prior therapy for AML with the exception of hydroxyurea and all-trans retinoic acid (ATRA), or leukapheresis. Patients with cytarabine-based emergency therapy prior to the start of therapy on this trial are eligible
* Patient must have no prior therapy with hypomethylating agents or FLT3 inhibitors
* Patient must have the FLT3-ITD or D835 mutation based on MyeloMATCH Master Screening and Reassessment Protocol (MSRP)
* Patient must be assigned to this protocol by the myeloMATCH MSRP
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
* All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
* A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Contraception measures must continue for 30 days after the last dose of venetoclax for all patients and for 6 months after the last dose of gilteritinib for patients of childbearing potential and for 4 months after the last dose of gilteritinib for male patients with partners of childbearing potential. Patient must not breastfeed during treatment and for 2 months after treatment ends
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Total bilirubin 2X ≤ institutional upper limit of normal (ULN) (unless thought to be elevated due to disease involvement or Gilbert's syndrome)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN
* Either measured or estimated by Cockcroft-Gault equation
* Creatinine clearance of ≥ 30 mL/min/1.73m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration/randomization are eligible for this trial
* Patients must not have a baseline corrected QT interval ≥ 480 msec using Fredericia correction (QTcF).
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patient must not have the medical necessity for ongoing treatment with a strong CYP3A4 inducing drug
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patients must not have an active or uncontrolled infection

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Principal Investigator

Jessica K Altman

PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Study Locations (Sites)

Yale University

New Haven, Connecticut, 06520

United States

Veterans Affairs Connecticut Healthcare System-West Haven Campus

West Haven, Connecticut, 06516

United States

Augusta University Medical Center

Augusta, Georgia, 30912

United States

Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712

United States

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, 83814

United States

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, 83619

United States

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, 83642

United States

Saint Alphonsus Cancer Care Center-Nampa

Nampa, Idaho, 83687

United States

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, 83687

United States

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, 83854

United States

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho, 83864

United States

Northwestern University

Chicago, Illinois, 60611

United States

Carle at The Riverfront

Danville, Illinois, 61832

United States

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, 62526

United States

Decatur Memorial Hospital

Decatur, Illinois, 62526

United States

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, 60115

United States

Carle Physician Group-Effingham

Effingham, Illinois, 62401

United States

Crossroads Cancer Center

Effingham, Illinois, 62401

United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, 60134

United States

Northwestern Medicine Glenview Outpatient Center

Glenview, Illinois, 60026

United States

Northwestern Medicine Grayslake Outpatient Center

Grayslake, Illinois, 60030

United States

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, 60045

United States

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, 61938

United States

Northwestern Medicine Orland Park

Orland Park, Illinois, 60462

United States

Memorial Hospital East

Shiloh, Illinois, 62269

United States

Southern Illinois University School of Medicine

Springfield, Illinois, 62702

United States

Springfield Clinic

Springfield, Illinois, 62702

United States

Springfield Memorial Hospital

Springfield, Illinois, 62781

United States

Carle Cancer Center

Urbana, Illinois, 61801

United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555

United States

University of Kansas Clinical Research Center

Fairway, Kansas, 66205

United States

University of Kansas Cancer Center

Kansas City, Kansas, 66160

United States

University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, 66211

United States

Cotton O'Neil Cancer Center / Stormont Vail Health

Topeka, Kansas, 66606

United States

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205

United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536

United States

The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, 40202

United States

UofL Health Medical Center Northeast

Louisville, Kentucky, 40245

United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, 48114

United States

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan, 48188

United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan, 48118

United States

Genesee Cancer and Blood Disease Treatment Center

Flint, Michigan, 48503

United States

Genesee Hematology Oncology PC

Flint, Michigan, 48503

United States

Genesys Hurley Cancer Institute

Flint, Michigan, 48503

United States

Hurley Medical Center

Flint, Michigan, 48503

United States

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, 48154

United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, 48197

United States

Baptist Memorial Hospital and Cancer Center-Golden Triangle

Columbus, Mississippi, 39705

United States

Baptist Cancer Center-Grenada

Grenada, Mississippi, 38901

United States

Baptist Memorial Hospital and Cancer Center-Union County

New Albany, Mississippi, 38652

United States

Baptist Memorial Hospital and Cancer Center-Oxford

Oxford, Mississippi, 38655

United States

Baptist Memorial Hospital and Cancer Center-Desoto

Southhaven, Mississippi, 38671

United States

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141

United States

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Siteman Cancer Center-South County

Saint Louis, Missouri, 63129

United States

Siteman Cancer Center at Christian Hospital

Saint Louis, Missouri, 63136

United States

Siteman Cancer Center at Saint Peters Hospital

Saint Peters, Missouri, 63376

United States

Billings Clinic Cancer Center

Billings, Montana, 59101

United States

Bozeman Health Deaconess Hospital

Bozeman, Montana, 59715

United States

Benefis Sletten Cancer Institute

Great Falls, Montana, 59405

United States

Logan Health Medical Center

Kalispell, Montana, 59901

United States

Community Medical Center

Missoula, Montana, 59804

United States

OptumCare Cancer Care at Seven Hills

Henderson, Nevada, 89052

United States

OptumCare Cancer Care at Charleston

Las Vegas, Nevada, 89102

United States

OptumCare Cancer Care at Fort Apache

Las Vegas, Nevada, 89148

United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106

United States

State University of New York Upstate Medical University

Syracuse, New York, 13210

United States

Duke University Medical Center

Durham, North Carolina, 27710

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104

United States

Providence Newberg Medical Center

Newberg, Oregon, 97132

United States

Providence Willamette Falls Medical Center

Oregon City, Oregon, 97045

United States

Providence Portland Medical Center

Portland, Oregon, 97213

United States

Providence Saint Vincent Medical Center

Portland, Oregon, 97225

United States

Geisinger Medical Center

Danville, Pennsylvania, 17822

United States

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104

United States

Reading Hospital

West Reading, Pennsylvania, 19611

United States

Prisma Health Cancer Institute - Spartanburg

Boiling Springs, South Carolina, 29316

United States

Prisma Health Cancer Institute - Easley

Easley, South Carolina, 29640

United States

Prisma Health Cancer Institute - Butternut

Greenville, South Carolina, 29605

United States

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, 29605

United States

Prisma Health Cancer Institute - Eastside

Greenville, South Carolina, 29615

United States

Prisma Health Cancer Institute - Greer

Greer, South Carolina, 29650

United States

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, 29672

United States

Baptist Memorial Hospital and Cancer Center-Collierville

Collierville, Tennessee, 38017

United States

Baptist Memorial Hospital and Cancer Center-Memphis

Memphis, Tennessee, 38120

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112

United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298

United States

ThedaCare Regional Cancer Center

Appleton, Wisconsin, 54911

United States

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601

United States

William S Middleton VA Medical Center

Madison, Wisconsin, 53705

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Jessica K Altman, PRINCIPAL_INVESTIGATOR, ECOG-ACRIN Cancer Research Group

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-27

Study Completion Date2025-10-31

Study Record Updates

Study Start Date2024-09-27

Study Completion Date2025-10-31

Terms related to this study

Additional Relevant MeSH Terms

Acute Myeloid Leukemia