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NCT02883049

PHASE3

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This randomized phase III trial studies how well combination chemotherapy works in treating young patients with newly diagnosed B acute lymphoblastic leukemia that is likely to come back or spread, and in patients with Philadelphia chromosome (Ph)-like tyrosine kinase inhibitor (TKI) sensitive mutations. 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. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.

Official title: A Phase III Randomized Trial for Newly Diagnosed High Risk B-Lymphoblastic Leukemia (B-ALL) Including a Stratum Evaluating Dasatinib (NSC#732517) in Patients With Ph-like Tyrosine Kinase Inhibitor (TKI) Sensitive Mutations

Key Details

Gender

All

Age Range

1 Year - 31 Years

Study Type

INTERVENTIONAL

Enrollment

5949

Start Date

2012-02-29

Completion Date

2026-03-31

Last Updated

2026-06-02

Healthy Volunteers

Conditions

B Acute Lymphoblastic Leukemia B Acute Lymphoblastic Leukemia, BCR-ABL1-Like Central Nervous System Leukemia Testicular Leukemia

Interventions

DRUG

Clofarabine

Given IV

DRUG

Cyclophosphamide

Given IV

DRUG

Cytarabine

Given IT, IV, or SC

DRUG

Dasatinib

Given PO

DRUG

Daunorubicin Hydrochloride

Given IV

DRUG

Dexamethasone

PO or IV

DRUG

Doxorubicin Hydrochloride

Given IV

DRUG

Etoposide

Given IV

DRUG

Hydrocortisone Sodium Succinate

Given IT

OTHER

Laboratory Biomarker Analysis

Correlative studies

DRUG

Leucovorin Calcium

Given PO or IV

DRUG

Mercaptopurine

Given PO

DRUG

Methotrexate

Given IT and IV

DRUG

Pegaspargase

Given IV

DRUG

Prednisone

Given PO or IV

RADIATION

Radiation Therapy

Undergo radiation therapy

DRUG

Thioguanine

Given PO

DRUG

Vincristine Sulfate

Given IV

Inclusion Criteria: * Patients must be enrolled on APEC14B1 and consented to Eligibility Screening on the Part A consent form prior to enrollment on AALL1131 * White Blood Cell Count (WBC) Criteria * Age 1-9.99 years: WBC \>= 50 000/uL * Age 10-30.99 years: Any WBC * Age 1-30.99 years: Any WBC with: * Testicular leukemia * CNS leukemia (CNS3) * Steroid pretreatment * Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization \[WHO\] classification) (also termed B-precursor acute lymphoblastic leukemia); patients with Down syndrome are also eligible * Organ function requirements for patients with Ph-like ALL and a predicted TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry onto the dasatinib arm of AALL1131 * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \> 70mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows: * Age: Maximum Serum Creatinine (mg/dL) * 1 to \< 6 months: 0.4 (male) 0.4 (female) * 6 months to \< 1 year: 0.5 (male) 0.5 (female) * 1 to \< 2 years: 0.6 (male) 0.6 (female) * 2 \< 6 years: 0.8 (male) 0.8 (female) * 6 to \< 10 years: 1.0 (male) 1.0 (female) * 10 to \< 13 years: 1.2 (male) 1.2 (female) * 13 to \< 16 years: 1.5 (male) 1.4 (female) * \> 16 years: 1.7 (male) 1.4 (female) * Direct bilirubin =\< 3 x upper limit of normal (ULN) for age, and * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 10 x upper limit of normal (ULN) for age * Shortening fraction \>= 27% by echocardiogram, or ejection fraction \>= 50% by gated radionuclide study * Patients must have an electrocardiogram (EKG) fewer than 6 days prior to enrollment on the dasatinib arm; patients who have had cardiac assessments by echocardiogram or radionuclide scan at the beginning of induction do not need to have these repeated prior to study entry; correct QT interval (QTc) \< 450 msec on baseline electrocardiogram as measured by the Friderica or Bazett formula * No major conduction abnormality (unless a cardiac pacemaker is present) * No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% at sea level if there is clinical indication for determination * Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, phenobarbital) should be avoided * Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive Functioning study * Patients must be aged 6 to 13 years at time of B-ALL diagnosis, enrolled on AALL1131 * Patients must be English-, French- or Spanish-speaking (languages in which the assessment is available) * Patients must have no known history of neurodevelopmental disorder prior to diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William's Syndrome, mental retardation) * Patients must have no significant visual impairment that would prevent computer use and recognition of the visual test stimuli * Eligibility criteria for the National Cancer Institute (NCI) standard risk patients from AALL0932 enrolling on this study at the end of Induction * Effective March 19, 2018, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the HR B-ALL stratum of this study at the end of Induction: * Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 8 peripheral blood (PB) minimal residual disease (MRD) \>= 1% and day 29 bone marrow (BM) MRD \< 0.01% * With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any day 8 PB MRD and day 29 BM MRD \>= 0.01% * Both NCI standard risk (SR) and HR patients without Down syndrome and with testicular disease at diagnosis, who do not meet other VHR criteria * Effective Amendment 6, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the VHR stratum of AALL1131: * Intrachromosomal amplification of chromosome 21 (iAMP21) * Mixed-lineage leukemia (MLL) rearrangement * Hypodiploidy (n \< 44 chromosomes and/or a deoxyribonucleic acid \[DNA\] index \< 0.81) * Induction failure (M3 BM at day 29) * Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 29 BM MRD \>= 0.01% * Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS HR B-ALL stratum of this study at the end of Induction: * Day 29 MRD \>= 0.01% * MLL rearrangement * Hypodiploidy (n \< 45 chromosomes and/or DNA index \< 0.81) * DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131) * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met Exclusion Criteria: * With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving prior steroid therapy may be eligible for AALL1131 * Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this study but may be eligible to enroll in a successor Children's Oncology Group (COG) Philadelphia positive (Ph+) ALL trial by day 15 Induction * DS HR B-ALL patients with Induction failure or BCR-ABL1 * Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs * Lactating females are not eligible unless they have agreed not to breastfeed their infant * Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained * Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

Locations (239)

Children's Hospital of Alabama

Birmingham, Alabama, United States

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

USA Health Strada Patient Care Center

Mobile, Alabama, United States

Providence Alaska Medical Center

Anchorage, Alaska, United States

Banner Children's at Desert

Mesa, Arizona, United States

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Kaiser Permanente Downey Medical Center

Downey, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Mattel Children's Hospital UCLA

Los Angeles, California, United States

Valley Children's Hospital

Madera, California, United States

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Children's Hospital of Orange County

Orange, California, United States

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Rady Children's Hospital - San Diego

San Diego, California, United States

Naval Medical Center -San Diego

San Diego, California, United States

UCSF Medical Center-Parnassus

San Francisco, California, United States

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Santa Barbara Cottage Hospital

Santa Barbara, California, United States

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Broward Health Medical Center

Fort Lauderdale, Florida, United States

Lee Memorial Health System

Fort Myers, Florida, United States

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

UF Health Cancer Institute - Gainesville

Gainesville, Florida, United States

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Palms West Radiation Therapy

Loxahatchee Groves, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Nicklaus Children's Hospital

Miami, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

AdventHealth Orlando