RECRUITING

Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)

Conditions

Quick Navigation

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 cytarabine with daunorubicin versus cytarabine with daunorubicin and venetoclax versus venetoclax with azacitidine for the treatment of younger patients with intermediate risk acute myeloid leukemia (AML). Cytarabine is a drug that inhibits some of the enzymes needed for deoxyribonucleic acid (DNA) replication and repair and can slow or stop the growth of cancer cells. Daunorubicin is a drug that blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. 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. Azacitidine is a drug that interacts with DNA to activate tumor-suppressing genes, resulting in an anti-tumor effect. Adding venetoclax to cytarabine and daunorubicin, and adding venetoclax to azacitidine, may work better than the usual treatment of cytarabine with daunorubicin alone. To decide if they are better, the study doctors are looking to see if venetoclax increases the rate of elimination of AML in participants by 20% or more compared to the usual approach.

Official Title

A Measurable Residual Disease (MRD) Driven, Phase II Study of Venetoclax Plus Chemotherapy for Newly Diagnosed Younger Patients With Intermediate Risk Acute Myeloid Leukemia: A Tier 1 MYELOMATCH Clinical Trial

Quick Facts

Study Start:2024-09-13

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05554393

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 to 59 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
* Patient must have enrolled onto MYELOMATCH and must have been given a treatment assignment to MyeloMATCH to MM1YA-CTG01 based on the presence of an actionable mutation as defined in MYELOMATCH * Participants must have been registered to master screening and re-assessment protocol (myeloMATCH MSRP) prior to consenting to this study. Participants must have been assigned to this clinical trial, via MATCHBox, prior to registration to this study. Participants must have agreed to have specimens submitted for translational medicine (MRD) and must be offered the opportunity to submit biosamples for banking for future research as per the myeloMATCH MSRP * Note: Pre-enrollment/diagnosis labs must have already been performed under the MSRP * Previously untreated, de novo acute myeloid leukemia (AML) defined by \> 20% myeloblasts in the peripheral blood or bone marrow (refer to the 2016 updated World Health Organization \[WHO\] classification of myeloid neoplasms and acute leukemia) excluding all the following categories of AML: * Favorable cytogenetics: (t(8;21)q22;q22.1); RUNX1-RUNX1T1, inversion 16(p13.1;q22), t(16;16)(p13.1;q22); CBFB-MYH11 * CEBPA biallelic mutations * NPM1 mutation * AML with PML-RARalpha * AML with any adverse cytogenetics, TP53 mutation, RUNX1 mutation, ASXL1, 11q23/KMT2 rearrangements * AML with FLT3-ITD or FLT3-TKD mutations * Therapy related AML, or AML following a diagnosis of myelodysplasia or myeloproliferative neoplasm Participants with central nervous system (CNS) disease are eligible for this trial and will be treated according to institutional guidelines with intrathecal chemotherapy for this aspect of their disease * Age 18-59 years at time of induction therapy * Eastern Cooperative Oncology Group (ECOG) performance status =\< 3 * Total bilirubin =\< 2 x institutional upper limit of normal (ULN) (must be done within 7 days of enrollment) * Aspartate aminotransferase (AST) (serum glutamate pyruvate transaminase \[SGPT\]) +/or alanine aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase \[SGOT\]) =\< 3 × institutional ULN (must be done within 7 days of enrollment) * Cardiac ejection fraction \>= 50% (echocardiography or multigated acquisition scan \[MUGA\]) (must be done within 7 days of enrollment) * Calculated creatinine clearance \>= 30 mL/min/ 1.73m\^2; Clearance to be calculated using Cockcroft formula (must be done within 7 days of enrollment) * White blood cells (WBC) must be \< 25 x 10\^9/L. Hydroxyurea and leukapheresis are permitted to control the WBC prior to enrollment and initiation of protocol-defined therapy but must be stopped at least 24 hours prior to the initiation of protocol therapy * 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 * Women/men of childbearing potential must have agreed to use a highly effective contraceptive method while on treatment and for 6 months after stopping study drug. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. * Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate * Patients must be accessible for treatment, response assessment and follow up. Patients enrolled on this trial must be treated and followed at the participating centre. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up. * In accordance with Canadian Cancer Trials Group (CCTG) policy, protocol treatment is to begin within 7 working days of patient enrollment * Participants receiving strong or moderate CYP3A inhibitors must agree to discontinue use at least 48 hours prior to start of study treatment if assigned to arm 1 or 2 * Patients with known human immunodeficiency virus (HIV) infection who are on effective anti-retroviral therapy and have undetectable viral load within 6 months of enrollment are eligible for this trial * Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days of enrollment. Patients need to be on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection who have been treated and cured are eligible. Patients who with active HCV infection who are currently being treated must have an undetectable HCV viral load within 28 days of enrollment to be eligible	* Prior therapy for AML except for hydroxyurea and leukapheresis to control blood counts. The use of all-trans retinoic acid (ATRA) is permitted until a diagnosis of acute promyelocytic leukemia, if suspected, is ruled out * Patients who are receiving any other investigational agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to cytarabine, daunorubicin, azacitidine, venetoclax * Pregnant women are excluded from this study because venetoclax, cytarabine and azacitidine have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, cytarabine and azacitidine breastfeeding should be discontinued if the mother is treated with venetoclax, cytarabine and azacitidine. These potential risks may also apply to other agents used in this study * Patients with isolated myeloid sarcoma are not eligible * Any other serious intercurrent illness, life threatening condition, organ system dysfunction, or medical condition judged by the local investigator to compromise the subject's safety (for example): * Active, uncontrolled bacterial, fungal, or viral infection

Inclusion Criteria

Exclusion Criteria

* Patient must have enrolled onto MYELOMATCH and must have been given a treatment assignment to MyeloMATCH to MM1YA-CTG01 based on the presence of an actionable mutation as defined in MYELOMATCH
* Participants must have been registered to master screening and re-assessment protocol (myeloMATCH MSRP) prior to consenting to this study. Participants must have been assigned to this clinical trial, via MATCHBox, prior to registration to this study. Participants must have agreed to have specimens submitted for translational medicine (MRD) and must be offered the opportunity to submit biosamples for banking for future research as per the myeloMATCH MSRP
* Note: Pre-enrollment/diagnosis labs must have already been performed under the MSRP
* Previously untreated, de novo acute myeloid leukemia (AML) defined by \> 20% myeloblasts in the peripheral blood or bone marrow (refer to the 2016 updated World Health Organization \[WHO\] classification of myeloid neoplasms and acute leukemia) excluding all the following categories of AML:
* Favorable cytogenetics: (t(8;21)q22;q22.1); RUNX1-RUNX1T1, inversion 16(p13.1;q22), t(16;16)(p13.1;q22); CBFB-MYH11
* CEBPA biallelic mutations
* NPM1 mutation
* AML with PML-RARalpha
* AML with any adverse cytogenetics, TP53 mutation, RUNX1 mutation, ASXL1, 11q23/KMT2 rearrangements
* AML with FLT3-ITD or FLT3-TKD mutations
* Therapy related AML, or AML following a diagnosis of myelodysplasia or myeloproliferative neoplasm Participants with central nervous system (CNS) disease are eligible for this trial and will be treated according to institutional guidelines with intrathecal chemotherapy for this aspect of their disease
* Age 18-59 years at time of induction therapy
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 3
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN) (must be done within 7 days of enrollment)
* Aspartate aminotransferase (AST) (serum glutamate pyruvate transaminase \[SGPT\]) +/or alanine aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase \[SGOT\]) =\< 3 × institutional ULN (must be done within 7 days of enrollment)
* Cardiac ejection fraction \>= 50% (echocardiography or multigated acquisition scan \[MUGA\]) (must be done within 7 days of enrollment)
* Calculated creatinine clearance \>= 30 mL/min/ 1.73m\^2; Clearance to be calculated using Cockcroft formula (must be done within 7 days of enrollment)
* White blood cells (WBC) must be \< 25 x 10\^9/L. Hydroxyurea and leukapheresis are permitted to control the WBC prior to enrollment and initiation of protocol-defined therapy but must be stopped at least 24 hours prior to the initiation of protocol therapy
* 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
* Women/men of childbearing potential must have agreed to use a highly effective contraceptive method while on treatment and for 6 months after stopping study drug. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures.
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
* Patients must be accessible for treatment, response assessment and follow up. Patients enrolled on this trial must be treated and followed at the participating centre. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* In accordance with Canadian Cancer Trials Group (CCTG) policy, protocol treatment is to begin within 7 working days of patient enrollment
* Participants receiving strong or moderate CYP3A inhibitors must agree to discontinue use at least 48 hours prior to start of study treatment if assigned to arm 1 or 2
* Patients with known human immunodeficiency virus (HIV) infection who are on effective anti-retroviral therapy and have undetectable viral load within 6 months of enrollment are eligible for this trial
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days of enrollment. Patients need to be on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection who have been treated and cured are eligible. Patients who with active HCV infection who are currently being treated must have an undetectable HCV viral load within 28 days of enrollment to be eligible

* Prior therapy for AML except for hydroxyurea and leukapheresis to control blood counts. The use of all-trans retinoic acid (ATRA) is permitted until a diagnosis of acute promyelocytic leukemia, if suspected, is ruled out
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cytarabine, daunorubicin, azacitidine, venetoclax
* Pregnant women are excluded from this study because venetoclax, cytarabine and azacitidine have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, cytarabine and azacitidine breastfeeding should be discontinued if the mother is treated with venetoclax, cytarabine and azacitidine. These potential risks may also apply to other agents used in this study
* Patients with isolated myeloid sarcoma are not eligible
* Any other serious intercurrent illness, life threatening condition, organ system dysfunction, or medical condition judged by the local investigator to compromise the subject's safety (for example):
* Active, uncontrolled bacterial, fungal, or viral infection

Contacts and Locations

Principal Investigator

Mary L Savoie

PRINCIPAL_INVESTIGATOR

Canadian Cancer Trials Group

Study Locations (Sites)

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

Centralia Oncology Clinic

Centralia, Illinois, 62801

United States

Northwestern University

Chicago, Illinois, 60611

United States

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, 62526

United States

Decatur Memorial Hospital

Decatur, Illinois, 62526

United States

Crossroads Cancer Center

Effingham, Illinois, 62401

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

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

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205

United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536

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

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104

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

Reading Hospital

West Reading, Pennsylvania, 19611

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

Inova Schar Cancer Institute

Fairfax, Virginia, 22031

United States

Inova Fairfax Hospital

Falls Church, Virginia, 22042

United States

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Mary L Savoie, PRINCIPAL_INVESTIGATOR, Canadian Cancer Trials 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 Date2024-09-13

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2024-09-13

Study Completion Date2025-12-31

Terms related to this study

Additional Relevant MeSH Terms

Acute Myeloid Leukemia