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Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia

RecruitingPhase 2

A Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax

Who can join

365 Days · All sexes

Full eligibility criteria
Inclusion Criteria:

* All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrollment on AALL2321
* Infants (aged 365 days or less) on the date of diagnosis are eligible; infants must be \> 36 weeks gestational age (cumulative prenatal and postnatal age must be \> 36 weeks) at the time of enrollment
* Patients must have newly diagnosed B-acute lymphoblastic leukemia (B-ALL, 2017 World Health Organization \[WHO\] classification), also termed B-precursor ALL, or acute leukemia of ambiguous lineage (ALAL), which includes mixed phenotype acute leukemia. For patients with ALAL, the immunophenotype of the leukemia must comprise at least 50% B lineage

  * Diagnostic immunophenotype: Leukemia cells must express CD19

Exclusion Criteria:

* Patients with Down Syndrome
* Patients with secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy
* Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of infant ALL or for any cancer diagnosis prior to the initiation of protocol therapy, with the exception of:

  * Steroid pretreatment:

    * PredniSONE, prednisoLONE, or methylPREDNISolone for ≤ 72 hours (3 days) in the 7 days prior to enrollment. The dose of predniSONE, prednisoLONE or methylPREDNISolone does not affect eligibility
    * Inhaled and topical steroids are not considered pretreatment
    * Note: Pretreatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone used during or within 6 hours prior to or after sedation to prevent or treat airway edema. However, prior exposure to ANY steroids that occurred \> 28 days before enrollment does not affect eligibility
  * Intrathecal cytarabine or methotrexate:

    * An intrathecal dose of cytarabine or methotrexate in the 7 days prior to enrollment does not affect eligibility
    * Note: The preference is to defer the diagnostic lumbar puncture with intrathecal chemotherapy to day 1 of induction to allow for cytoreduction of circulating blasts and decrease the potential for central nervous system (CNS) contamination due to a traumatic tap. If done prior to day 1 of induction, these results will be used to determine CNS status
  * Hydroxyurea:

    * Pretreatment with ≤ 72 hours (3 days) of hydroxyurea in the 7 days prior to enrollment does not affect eligibility
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA) and National Cancer Institute (NCI) requirements for human studies must be met

About the study

This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged \[R\]) or without a KMT2A gene rearrangement (KMT2A-germline \[G\]). 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. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.

What is being tested

Sponsor: National Cancer Institute (NCI) · Participants: 153 · Started: Jun 5, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT06317662

Locations in the U.S.

AlabamaChildren's Hospital of Alabama, Birmingham
AlaskaProvidence Alaska Medical Center, Anchorage
ArizonaBanner Children's at Desert, Mesa
ArkansasArkansas Children's Hospital, Little Rock
CaliforniaLoma Linda University Medical Center, Loma Linda
Miller Children's and Women's Hospital Long Beach, Long Beach
Kaiser Permanente-Oakland, Oakland
UCSF Benioff Children's Hospital Oakland, Oakland
Children's Hospital of Orange County, Orange
University of California Davis Comprehensive Cancer Center, Sacramento
UCSF Medical Center-Mission Bay, San Francisco
ColoradoChildren's Hospital Colorado, Aurora
ConnecticutYale University, New Haven
DelawareAlfred I duPont Hospital for Children, Wilmington
District of ColumbiaChildren's National Medical Center, Washington D.C.
FloridaUF Health Cancer Institute - Gainesville, Gainesville
Memorial Regional Hospital/Joe DiMaggio Children's Hospital, Hollywood
Nemours Children's Clinic-Jacksonville, Jacksonville
University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami
AdventHealth Orlando, Orlando
Arnold Palmer Hospital for Children, Orlando
Nemours Children's Hospital, Orlando
Nemours Children's Clinic - Pensacola, Pensacola
Johns Hopkins All Children's Hospital, St. Petersburg
Saint Joseph's Hospital/Children's Hospital-Tampa, Tampa
Saint Mary's Medical Center, West Palm Beach
GeorgiaChildren's Healthcare of Atlanta - Arthur M Blank Hospital, Atlanta
HawaiiKapiolani Medical Center for Women and Children, Honolulu
IdahoSaint Luke's Cancer Institute - Boise, Boise
IllinoisLurie Children's Hospital-Chicago, Chicago
University of Chicago Comprehensive Cancer Center, Chicago
Advocate Children's Hospital-Oak Lawn, Oak Lawn
Advocate Children's Hospital-Park Ridge, Park Ridge
OSF Children's Hospital of Illinois, Peoria
Southern Illinois University School of Medicine, Springfield
IndianaRiley Hospital for Children, Indianapolis
IowaBlank Children's Hospital, Des Moines
KentuckyUniversity of Kentucky/Markey Cancer Center, Lexington
Norton Children's Hospital, Louisville
LouisianaChildren's Hospital New Orleans, New Orleans
Ochsner Medical Center Jefferson, New Orleans
MaineMaine Children's Cancer Program, Scarborough
MarylandJohns Hopkins University/Sidney Kimmel Cancer Center, Baltimore
Sinai Hospital of Baltimore, Baltimore
MassachusettsDana-Farber Cancer Institute, Boston
UMass Memorial Medical Center - University Campus, Worcester
MichiganC S Mott Children's Hospital, Ann Arbor
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital, Grand Rapids
Bronson Methodist Hospital, Kalamazoo
MinnesotaUniversity of Minnesota/Masonic Cancer Center, Minneapolis
MississippiUniversity of Mississippi Medical Center, Jackson
MissouriChildren's Mercy Hospitals and Clinics, Kansas City
Mercy Hospital Saint Louis, St Louis
Washington University School of Medicine, St Louis
NebraskaChildren's Hospital and Medical Center of Omaha, Omaha
NevadaAlliance for Childhood Diseases/Cure 4 the Kids Foundation, Las Vegas
New HampshireDartmouth Hitchcock Medical Center/Dartmouth Cancer Center, Lebanon
New JerseyHackensack University Medical Center, Hackensack
Morristown Medical Center, Morristown
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital, New Brunswick
Saint Joseph's Regional Medical Center, Paterson
New YorkAlbany Medical Center, Albany
Roswell Park Cancer Institute, Buffalo
The Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park
Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York
Memorial Sloan Kettering Cancer Center, New York
NYP/Weill Cornell Medical Center, New York
University of Rochester, Rochester
State University of New York Upstate Medical University, Syracuse
Montefiore Medical Center - Moses Campus, The Bronx
New York Medical College, Valhalla
North CarolinaUNC Lineberger Comprehensive Cancer Center, Chapel Hill
Carolinas Medical Center/Levine Cancer Institute, Charlotte
Duke University Medical Center, Durham
East Carolina University, Greenville
Wake Forest University Health Sciences, Winston-Salem
North DakotaSanford Broadway Medical Center, Fargo
OhioChildren's Hospital Medical Center of Akron, Akron
Cincinnati Children's Hospital Medical Center, Cincinnati
Rainbow Babies and Childrens Hospital, Cleveland
Dayton Children's Hospital, Dayton
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital, Toledo
OklahomaUniversity of Oklahoma Health Sciences Center, Oklahoma City
PennsylvaniaLehigh Valley Hospital-Cedar Crest, Allentown
Geisinger Medical Center, Danville
Penn State Children's Hospital, Hershey
Children's Hospital of Philadelphia, Philadelphia
Children's Hospital of Pittsburgh of UPMC, Pittsburgh
Rhode IslandRhode Island Hospital, Providence
South CarolinaPrisma Health Richland Hospital, Columbia
BI-LO Charities Children's Cancer Center, Greenville
South DakotaSanford USD Medical Center - Sioux Falls, Sioux Falls
TennesseeEast Tennessee Childrens Hospital, Knoxville
Saint Jude Children's Research Hospital, Memphis
The Children's Hospital at TriStar Centennial, Nashville
Vanderbilt University/Ingram Cancer Center, Nashville
TexasDell Children's Medical Center of Central Texas, Austin
Driscoll Children's Hospital, Corpus Christi
Medical City Dallas Hospital, Dallas
UT Southwestern/Simmons Cancer Center-Dallas, Dallas
El Paso Children's Hospital, El Paso
Cook Children's Medical Center, Fort Worth
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center, Houston
Children's Hospital of San Antonio, San Antonio
Methodist Children's Hospital of South Texas, San Antonio
Scott and White Memorial Hospital, Temple
VirginiaUniversity of Virginia Cancer Center, Charlottesville
Children's Hospital of The King's Daughters, Norfolk
VCU Massey Comprehensive Cancer Center, Richmond
Carilion Children's, Roanoke
WashingtonSeattle Children's Hospital, Seattle
Providence Sacred Heart Medical Center and Children's Hospital, Spokane
WisconsinSaint Vincent Hospital Cancer Center Green Bay, Green Bay
Children's Hospital of Wisconsin, Milwaukee

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.