Blood Cancer

EA9181



Testing the Use of Steroids and Tyrosine Kinase Inhibitors with Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults

STATUS: Active


This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager (โ€˜BiTEโ€™) that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.
  • ELIGIBILITY CRITERIA FOR PREREGISTRATION (TO STEP 0) - INCLUSION

  • Patient must be >= 18 and =< 75 years of age

  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-3

  • Patient must be newly diagnosed with B-ALL or is suspected to have ALL * Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin Step 1 therapy while awaiting central laboratory eligibility confirmation ** NOTE: Bone marrow aspirate and/or peripheral blood specimen must be submitted to the American College of Radiology Imaging Network (ECOG-ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patientโ€™s eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow aspirate is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, given that adequate circulating blasts are present (> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to Step 1 without waiting for central confirmation

  • Patients who started any kind of TKI prior to study registration to Step 1 are allowed to proceed on the study if they received no more than 14 days of TKI

  • ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1 - INCLUSION

  • Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has been determined locally, and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center

  • Total bilirubin =< 3 mg/dL (patients with Gilbertโ€™s syndrome must have a total bilirubin =< 5 mg/dL) (obtained =< 28 days prior to step 1 registration)

  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X the institutional upper limit of normal (ULN) (obtained =< 28 days prior to step 1 registration)

  • Estimated creatinine clearance > 45 mL/min (based on Cockcroft-Gault equation) (obtained =< 28 days prior to step 1 registration)

  • Patients with acute organ dysfunction at step 1 registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to Step 2 randomization if the eligibility criteria outlined is met

  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated

  • Patients who presented with no evidence of acute organ dysfunction but during Step 0 experienced a rise in liver enzymes which investigator suspects to be a side effect of any of prescribed drugs, are allowed to be registered regardless of the level of liver enzymes. Step 2 Randomization must be withheld until the eligibility criteria outline is met but no more than 14 days after concluding Arm A therapy

  • Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment

  • Patients with a prior 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 must be class 2B or better. An ECHO/MUGA is required.

  • 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 must be class 2B or better

  • Investigators must confirm which TKI patient is to receive * NOTE: Patients with known T315I mutation status should receive ponatinib treatment * NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during Step 1. The investigator must re-specify dasatinib or ponatinib prior to Step 2 randomization and from then on patients must receive the pre-selected TKI only

  • ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2- INCLUSION

  • Patient must have completed at least 7 and no more than 21 days of protocol-treatment on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for any reason are not counted) * NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI must be initiated prior to randomization

  • Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =< 2 X institutional upper limit of normal (ULN)

  • AST(SGOT)/ ALT(SGPT) =< 2 X the institutional upper limit of normal (ULN)

  • Estimated creatinine clearance > 45 mLg/min (based on Cockcroft-Gault equation)

  • Investigators must confirm which TKI patient is to receive. * NOTE: Patients with known T315I mutation status should receive ponatinib treatment

  • For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization

  • Patients must have resolved any serious infectious complications related to therapy

  • Any significant medical complications related to therapy must have resolved

  • ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION) - INCLUSION

  • Institution has received centralized MRD results confirming positive status

  • Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =< 2 X institutional ULN

  • Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =< 2 X institutional upper limit of normal (ULN)

  • Patients who presented with acute organ dysfunction must have an estimated creatinine clearance > 45 mL/min (based on Cockcroft-Gault equation)

  • Investigators must confirm which TKI patient is to receive * NOTE: Patients with known T315I mutation status should receive ponatinib treatment

  • For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined

  • PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA - EXCLUSION

  • Patient must not have a diagnosis of BCR/ABL T-ALL

  • Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of hydroxyurea or steroids of any kind with the aim to reduce disease burden prior to study registration to Step 1 are eligible

  • Patient must not have unstable epilepsy that requires treatment

  • Patients with lymphoid blast crisis CML are not eligible

  • STEP 1 REGISTRATION ELIGIBILITY CRITERIA - EXCLUSION

  • 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 any woman, 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)

  • Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment

  • Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies are eligible

  • Patient must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol

  • STEP 2: RANDOMIZATION - ELIGIBILITY CRITERIA - EXCLUSION

  • Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated

Israel
Jerusalem
Shaare Zedek Medical Center
Status: ACTIVE
Contact: Site Public Contact

United States
AK
Anchorage
Alaska Breast Care and Surgery LLC
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Alaska Oncology and Hematology LLC
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Alaska Women's Cancer Care
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Anchorage Associates in Radiation Medicine
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
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Email: AKPAMC.OncologyResearchSupport@providence.org

Anchorage Oncology Centre
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Anchorage Radiation Therapy Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Katmai Oncology Group
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Providence Alaska Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
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Email: AKPAMC.OncologyResearchSupport@providence.org

AR
Ft. Smith
Mercy Hospital Fort Smith
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

CA
Burbank
Providence Saint Joseph Medical Center / Disney Family Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: Najee.Boucher@providence.org

Clovis
Community Cancer Institute
Status: ACTIVE
Contact: Site Public Contact

University Oncology Associates
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

La Jolla
UC San Diego Moores Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: cancercto@ucsd.edu

Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: ucstudy@uci.edu

GA
Augusta
Augusta University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: ga_cares@augusta.edu

HI
Aiea
Hawaii Cancer Care - Savio
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: info@hawaiicancercare.com

Pali Momi Medical Center
Status: ACTIVE
Contact: Site Public Contact

Queen's Cancer Center - Pearlridge
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

The Cancer Center of Hawaii-Pali Momi
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Honolulu
Hawaii Cancer Care Inc - Waterfront Plaza
Status: ACTIVE
Contact: Site Public Contact
Email: i.webster@hawaiicancercare.com

Hawaii Cancer Care Inc-Liliha
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Kapiolani Medical Center for Women and Children
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Kuakini Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Queen's Cancer Cenrer - POB I
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Queen's Cancer Center - Kuakini
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
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Queen's Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Straub Clinic and Hospital
Status: ACTIVE
Contact: Site Public Contact

The Cancer Center of Hawaii-Liliha
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

University of Hawaii Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Lihue
Wilcox Memorial Hospital and Kauai Medical Clinic
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

IA
Ames
Mary Greeley Medical Center
Status: ACTIVE
Contact: Site Public Contact

McFarland Clinic PC - Ames
Status: ACTIVE
Contact: Site Public Contact
Email: ksoder@mcfarlandclinic.com

Boone
McFarland Clinic PC-Boone
Status: ACTIVE
Contact: Site Public Contact

Fort Dodge
McFarland Clinic PC-Trinity Cancer Center
Status: ACTIVE
Contact: Site Public Contact

Jefferson
McFarland Clinic PC-Jefferson
Status: ACTIVE
Contact: Site Public Contact

Marshalltown
McFarland Clinic PC-Marshalltown
Status: ACTIVE
Contact: Site Public Contact

ID
Boise
Saint Luke's Cancer Institute - Boise
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: eslinget@slhs.org

Fruitland
Saint Luke's Cancer Institute - Fruitland
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: eslinget@slhs.org

Meridian
Saint Luke's Cancer Institute - Meridian
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: eslinget@slhs.org

Nampa
Saint Luke's Cancer Institute - Nampa
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: eslinget@slhs.org

Twin Falls
Saint Luke's Cancer Institute - Twin Falls
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: eslinget@slhs.org

IL
Alton
Saint Anthony's Health
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Burr Ridge
Loyola Center for Health at Burr Ridge
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Chicago
Northwestern University
Status: ACTIVE
Contact: Site Public Contact
Email: cancer@northwestern.edu

Evanston
NorthShore University HealthSystem-Evanston Hospital
Status: ACTIVE
Contact: Site Public Contact

Glenview
NorthShore University HealthSystem-Glenbrook Hospital
Status: ACTIVE
Contact: Site Public Contact

Highland Park
NorthShore University HealthSystem-Highland Park Hospital
Status: ACTIVE
Contact: Site Public Contact

Homer Glen
Loyola Medicine Homer Glen
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Lake Forest
Northwestern Medicine Lake Forest Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cancertrials@northwestern.edu

Maywood
Loyola University Medical Center
Status: ACTIVE
Contact: Site Public Contact

Melrose Park
Marjorie Weinberg Cancer Center at Loyola-Gottlieb
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Mount Vernon
Good Samaritan Regional Health Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

KS
Garden City
Central Care Cancer Center - Garden City
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: aroland@kccop.org

Great Bend
Central Care Cancer Center - Great Bend
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: aroland@kccop.org

Kansas City
University of Kansas Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

Overland Park
University of Kansas Hospital-Indian Creek Campus
Status: ACTIVE
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: KUCC_Navigation@kumc.edu

KY
Louisville
The James Graham Brown Cancer Center at University of Louisville
Status: ACTIVE
Contact: Site Public Contact

LA
Shreveport
LSU Health Sciences Center at Shreveport
Status: ACTIVE
Contact: Site Public Contact
Email: LPost@lsuhsc.edu

MD
Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: jhcccro@jhmi.edu

Bethesda
Walter Reed National Military Medical Center
Status: ACTIVE
Contact: Site Public Contact

MI
Brownstown
Henry Ford Cancer Institute-Downriver
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CTOResearch@hfhs.org

Clinton Township
Henry Ford Macomb Hospital-Clinton Township
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CTOResearch@hfhs.org

Dearborn
Henry Ford Medical Center-Fairlane
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CTOResearch@hfhs.org

Detroit
Henry Ford Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: CTOResearch@hfhs.org

Wayne State University / Karmanos Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Email: ctoadmin@karmanos.org

Farmington Hills
Weisberg Cancer Treatment Center
Status: ACTIVE
Contact: Site Public Contact
Email: ctoadmin@karmanos.org

Jackson
Allegiance Health
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CTOResearch@hfhs.org

Novi
Henry Ford Medical Center-Columbus
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CTOResearch@hfhs.org

Shelby Township
Henry Ford Macomb Health Center - Shelby Township
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: tpearce1@hfhs.org

West Bloomfield
Henry Ford West Bloomfield Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CTOResearch@hfhs.org

MN
Rochester
Mayo Clinic in Rochester
Status: ACTIVE
Contact: Site Public Contact

MO
Ballwin
Saint Louis Cancer and Breast Institute-Ballwin
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Bolivar
Central Care Cancer Center - Bolivar
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: aroland@kccop.org

Creve Coeur
Siteman Cancer Center at West County Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Joplin
Freeman Health System
Status: ACTIVE
Contact: Site Public Contact
Email: LJCrockett@freemanhealth.com

Mercy Hospital Joplin
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: esmeralda.carrillo@mercy.net

Kansas City
Research Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: aroland@kccop.org

Rolla
Delbert Day Cancer Institute at PCRMC
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: research@phelpshealth.org

Mercy Clinic-Rolla-Cancer and Hematology
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Saint Joseph
Heartland Regional Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: linda.schumacher@mymlc.com

Saint Louis
Mercy Hospital Saint Louis
Status: ACTIVE
Contact: Site Public Contact

Mercy Hospital South
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: janet.lesko@mercy.net

Saint Louis Cancer and Breast Institute-South City
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Siteman Cancer Center at Christian Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Siteman Cancer Center-South County
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Washington University School of Medicine
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Saint Peters
Siteman Cancer Center at Saint Peters Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Springfield
CoxHealth South Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Mercy Hospital Springfield
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Washington
Mercy Hospital Washington
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

MS
Southhaven
Baptist Memorial Hospital and Cancer Center-Desoto
Status: ACTIVE
Contact: Site Public Contact
Email: BCCclintrials@bmhcc.org

MT
Missoula
Saint Patrick Hospital - Community Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: amy.hanneman@providence.org

NC
Durham
Duke University Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Winston-Salem
Wake Forest University Health Sciences
Status: ACTIVE
Contact: Site Public Contact

NJ
New Brunswick
Rutgers Cancer Institute of New Jersey
Status: ACTIVE
Contact: Site Public Contact

NY
Bronx
Montefiore Medical Center - Moses Campus
Status: ACTIVE
Contact: Site Public Contact
Email: eskwak@montefiore.org

Rochester
University of Rochester
Status: ACTIVE
Contact: Site Public Contact

OH
Cincinnati
University of Cincinnati Cancer Center-UC Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cancer@uchealth.com

Cleveland
MetroHealth Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: dstrater@metrohealth.org

Columbus
Ohio State University Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: Jamesline@osumc.edu

West Chester
University of Cincinnati Cancer Center-West Chester
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cancer@uchealth.com

OK
Oklahoma City
Mercy Hospital Oklahoma City
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

University of Oklahoma Health Sciences Center
Status: ACTIVE
Contact: Site Public Contact
Email: ou-clinical-trials@ouhsc.edu

OR
Bend
Saint Charles Health System
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: nosall@stcharleshealthcare.org

Clackamas
Clackamas Radiation Oncology Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Providence Cancer Institute Clackamas Clinic
Status: ACTIVE
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Coos Bay
Bay Area Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cherie.cox@bayareahospital.org

Newberg
Providence Newberg Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Portland
Providence Portland Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Providence Saint Vincent Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Redmond
Saint Charles Health System-Redmond
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

PA
Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE
Contact: Site Public Contact

SC
Boiling Springs
Prisma Health Cancer Institute - Spartanburg
Status: ACTIVE
Contact: Site Public Contact

Easley
Prisma Health Cancer Institute - Easley
Status: ACTIVE
Contact: Site Public Contact
Email: Kim.Williams3@prismahealth.org

Greenville
Prisma Health Cancer Institute - Butternut
Status: ACTIVE
Contact: Site Public Contact

Prisma Health Cancer Institute - Eastside
Status: ACTIVE
Contact: Site Public Contact

Prisma Health Cancer Institute - Faris
Status: ACTIVE
Contact: Site Public Contact

Prisma Health Greenville Memorial Hospital
Status: ACTIVE
Contact: Site Public Contact

Greer
Prisma Health Cancer Institute - Greer
Status: ACTIVE
Contact: Site Public Contact

Seneca
Prisma Health Cancer Institute - Seneca
Status: ACTIVE
Contact: Site Public Contact

TN
Franklin
Vanderbilt-Ingram Cancer Center Cool Springs
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Memphis
Baptist Memorial Hospital and Cancer Center-Memphis
Status: ACTIVE
Contact: Site Public Contact
Email: BCCclintrials@bmhcc.org

Nashville
Vanderbilt Breast Center at One Hundred Oaks
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Vanderbilt University / Ingram Cancer Center
Status: ACTIVE
Contact: Site Public Contact

TX
Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Site Public Contact
Email: canceranswerline@UTSouthwestern.edu

VA
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: CTOclinops@vcu.edu

WI
Eau Claire
Marshfield Medical Center-EC Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

La Crosse
Gundersen Lutheran Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: cancerctr@gundersenhealth.org

Marshfield
Marshfield Medical Center-Marshfield
Status: ACTIVE
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Milwaukee
Medical College of Wisconsin
Status: ACTIVE
Contact: Site Public Contact

Minocqua
Marshfield Clinic-Minocqua Center
Status: ACTIVE
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Rice Lake
Marshfield Medical Center-Rice Lake
Status: ACTIVE
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Stevens Point
Marshfield Medical Center-River Region at Stevens Point
Status: ACTIVE
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Weston
Marshfield Medical Center - Weston
Status: ACTIVE
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

PRIMARY OBJECTIVE:
I. To compare the overall survival (OS) following induction with steroids + TKI + blinatumomab versus induction with steroids + TKI + chemotherapy.

SECONDARY OBJECTIVES:
I. To compare the rate of minimal residual disease (MRD) negativity for patients treated with chemotherapy versus (vs) blinatumomab at the end of first induction (week 15).
II. To evaluate the rate of the MRD negativity by treatment arm for those patients MRD positive after the first induction and administered of second induction.
III. To compare event free survival (EFS) for patients initially randomized for chemotherapy vs blinatumomab.
IV. To assess the toxicities of blinatumomab + TKI vs. TKI + chemotherapy in this patient population.
V. To assess the toxicities of the chemotherapy regimen in this patient population.
VI. To describe the outcome of patients who proceed to allogeneic stem cell transplant after treatment with blinatumomab + TKI only.

OUTLINE:

ARM A (PRE-INDUCTION): Patients receive prednisone orally (PO) once daily (QD) on days 1-21 and ponatinib hydrochloride (ponatinib) PO QD or dasatinib PO QD on days 1-21 based on investigator's choice.

Patients are randomized to 1 of 2 arms (Arm B or C). Patients will undergo bone marrow aspiration with biopsy, lumbar punctures, echocardiogram (ECHO), and multigated acquisition (MUGA) scans as indicated by investigator.

ARM B (INDUCTION THERAPY): 

CYCLE 1: Patients receive cyclophosphamide intravenously (IV) twice daily (BID) on days 1-3, dexamethasone PO or IV on days 1-4 and 11-14, cytarabine intrathecally (IT) on day 1, doxorubicin hydrochloride (doxorubicin) IV on day 4, vincristine sulfate (vincristine) IV on days 4 and 11, and methotrexate IT on day 8. Patients also receive Mesna 600mg/m^2 IV as a โ€˜chemoprotectantโ€™ via continuous infusion on days 1-3, (beginning 1 hour prior to cyclophosphamide and completed by 12 hours after the last dose of cyclophosphamide). 

CYCLE 2 (AGE 18-70): Starting in cycle 2, fit patients aged 18-70 receive dasatinib 70mg/day PO or ponatinib 30mg/day PO on days 1-21, methotrexate IV over 24 hours and IT on day 1, and cytarabine IV over 2 hours on days 2-3 of each cycle. On day 22 of cycle 2 or later, as soon as the absolute neutrophil count (ANC) is greater than 1000 cells/ul and platelets are greater than 50,000 cells/ul, patients receive hyper cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) for 2 additional cycles.

CYCLE 2 (AGE > 70 or unfit < 70): Starting in cycle 2, patients age > 70 or younger unfit patients for Hyper-CVAD receive ponatinib PO QD or dasatinib PO QD on days 1-21 of each cycle. Patients also receive methotrexate IV over 24 hours and IT on day 1, and cytarabine IV over 2 hours on days 2-3 of each cycle. Cycle 1 and 2 regimens are each repeated once starting on day 22 of cycle 2, or later, but as soon as the ANC is greater than 1000 cells/ul and platelets are greater than 50,000 cells/ul.

Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve remission (significant reduction in the amount of leukemia in bone marrow and blood/MRD negative) after 4 cycles may receive alternative treatment, either consolidation with two cycles of Hyper-CVAD followed by TKI maintenance therapy or undergo allogeneic stem cell transplantation followed by maintenance therapy. Patients who do not achieve a remission (MRD positive) are assigned to Arm D. Patients who experience un-resolving renal failure or life-threatening infection which may require a treatment delay of 21 days cross-over to Arm C to receive the prescribed course of blinatumomab. 

ARM C (INDUCTION THERAPY):

CYCLE 1: Patients receive ponatinib PO QD or dasatinib PO QD on days 1-28. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28, followed by methotrexate IT on day 28 or 29.

CYCLE 2: Patients receive ponatinib PO QD or dasatinib PO QD on days 1-28. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28.

Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

ARM D (RE-INDUCTION): Patients treated on Arm B who remain MRD positive at the end of induction therapy receive blinatumomab based re-induction identical to the regimen described for Arm C.

ARM E (RE-INDUCTION): Patients treated on Arm C who remain MRD positive at the end of induction therapy receive chemotherapy based re-induction which is identical to regimen described for Arm B according to patient's age and the pre-specified chemotherapy arm.

Patients whose molecular test remains MRD positive after re-induction proceed to follow-up at the discretion of the investigator or receive anti CD-19 CAR- T cell therapy, inotuzumab ozogamicin, intensive chemotherapy, or palliative care.

Patients are followed up for 10 years from the date of registration.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its National Clinical Trials Network.


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