B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1Phase 3NCT04530565
Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
A Phase 3 study testing Biospecimen Collection, Blinatumomab and Bone Marrow Aspiration and Biopsy in people with B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, run by National Cancer Institute (NCI) at 211 sites in 3 countries.
Trial summary
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 ('BiTE') that may interfere with the ability of cancer cells to grow and spread. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
- What is being tested?
- Biospecimen Collection, Blinatumomab and Bone Marrow Aspiration and Biopsy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 348 participants
- Where
- 211 sitesin 3 countries
- Study dates
- 25 Jan 2021to 1 Jul 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ELIGIBILITY CRITERIA FOR PRE-REGISTRATION (TO STEP 0)
- 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 acute lymphoblastic leukemia (B-ALL) or is suspected to have acute lymphoblastic leukemia (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 ECOG-American College of Radiology Imaging Network (ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient'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, with recommendation 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
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- 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 therapy (hydroxyurea and/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 chronic myeloid leukemia (CML) are not eligible
- ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
- 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
- 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 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
- Total bilirubin =< 3 mg/dL (patients with Gilbert'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]) and 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
- 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
- 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 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
- 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
- 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
- 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) and ALT(SGPT) =< 2 X the institutional upper limit of normal (ULN)
- 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, intended chemotherapy regimen must have been determined prior to randomization
- 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
- 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)
- 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
- Step 3 (Re-Induction): Patients must have resolved any serious infectious complications related to therapy
- Step 3 (Re-Induction): Any significant medical complications related to therapy must have resolved
Who cannot join
None listed.
Trial locations and contacts
211 sites in 3 countries.
211 sites in 3 countries
United States207 sites
Hawaii Cancer Care - Westridge
‘Aiea, Hawaii, 96701
Pali Momi Medical Center
‘Aiea, Hawaii, 96701
Queen's Cancer Center - Pearlridge
‘Aiea, Hawaii, 96701
The Cancer Center of Hawaii-Pali Momi
‘Aiea, Hawaii, 96701
Providence Regional Cancer System-Aberdeen
Aberdeen, Washington, 98520
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
OSF Saint Anthony's Health Center
Alton, Illinois, 62002
Mary Greeley Medical Center
Ames, Iowa, 50010
McFarland Clinic - Ames
Ames, Iowa, 50010
Anchorage Associates in Radiation Medicine
Anchorage, Alaska, 98508
Anchorage Radiation Therapy Center
Anchorage, Alaska, 99504
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, 99508
Alaska Oncology and Hematology LLC
Anchorage, Alaska, 99508
Alaska Women's Cancer Care
Anchorage, Alaska, 99508
Anchorage Oncology Centre
Anchorage, Alaska, 99508
Katmai Oncology Group
Anchorage, Alaska, 99508
Providence Alaska Medical Center
Anchorage, Alaska, 99508
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Augusta University Medical Center
Augusta, Georgia, 30912
Mercy Oncology and Hematology - Clayton-Clarkson
Ballwin, Missouri, 63011
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
PeaceHealth Saint Joseph Medical Center
Bellingham, Washington, 98225
Saint Charles Health System
Bend, Oregon, 97701
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Central Care Cancer Center - Bolivar
Bolivar, Missouri, 65613
McFarland Clinic - Boone
Boone, Iowa, 50036
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, 91505
University of Vermont Medical Center
Burlington, Vermont, 05401
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
Loyola Center for Health at Burr Ridge
Burr Ridge, Illinois, 60527
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Providence Regional Cancer System-Centralia
Centralia, Washington, 98531
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Northwestern University
Chicago, Illinois, 60611
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015
Providence Cancer Institute Clackamas Clinic
Clackamas, Oregon, 97015
Hematology Oncology Consultants-Clarkston
Clarkston, Michigan, 48346
Newland Medical Associates-Clarkston
Clarkston, Michigan, 48346
Case Western Reserve University
Cleveland, Ohio, 44106
MetroHealth Medical Center
Cleveland, Ohio, 44109
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
Community Cancer Institute
Clovis, California, 93611
University Oncology Associates
Clovis, California, 93611
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Bay Area Hospital
Coos Bay, Oregon, 97420
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Geisinger Medical Center
Danville, Pennsylvania, 17822
Henry Ford Medical Center-Fairlane
Dearborn, Michigan, 48126
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640
Pocono Medical Center
East Stroudsburg, Pennsylvania, 18301
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201
Providence Regional Cancer Partnership
Everett, Washington, 98201
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
Cancer Hematology Centers - Flint
Flint, Michigan, 48503
Genesee Hematology Oncology PC
Flint, Michigan, 48503
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501
Mercy Hospital Fort Smith
Fort Smith, Arkansas, 72903
Vanderbilt-Ingram Cancer Center Cool Springs
Franklin, Tennessee, 37067
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
Central Care Cancer Center - Garden City
Garden City, Kansas, 67846
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, 60026
Central Care Cancer Center - Great Bend
Great Bend, Kansas, 67530
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Prisma Health Greenville Memorial Hospital
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650
Lehigh Valley Hospital-Hazleton
Hazleton, Pennsylvania, 18201
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, 60035
Loyola Medicine Homer Glen
Homer Glen, Illinois, 60491
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu, Hawaii, 96813
Queen's Cancer Cenrer - POB I
Honolulu, Hawaii, 96813
Queen's Medical Center
Honolulu, Hawaii, 96813
Straub Clinic and Hospital
Honolulu, Hawaii, 96813
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
Hawaii Cancer Care Inc-Liliha
Honolulu, Hawaii, 96817
Kuakini Medical Center
Honolulu, Hawaii, 96817
Queen's Cancer Center - Kuakini
Honolulu, Hawaii, 96817
The Cancer Center of Hawaii-Liliha
Honolulu, Hawaii, 96817
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Houston Methodist Hospital
Houston, Texas, 77030
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029
Allegiance Health
Jackson, Michigan, 49201
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129
Freeman Health System
Joplin, Missouri, 64804
Mercy Hospital Joplin
Joplin, Missouri, 64804
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Research Medical Center
Kansas City, Missouri, 64132
Kadlec Clinic Hematology and Oncology
Kennewick, Washington, 99336
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Providence Regional Cancer System-Lacey
Lacey, Washington, 98503
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045
Wilcox Memorial Hospital and Kauai Medical Clinic
Lihue, Hawaii, 96766
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Monmouth Medical Center
Long Branch, New Jersey, 07740
PeaceHealth Saint John Medical Center
Longview, Washington, 98632
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202
UofL Health Medical Center Northeast
Louisville, Kentucky, 40245
Henry Ford Saint John Hospital - Macomb Medical
Macomb, Michigan, 48044
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Loyola University Medical Center
Maywood, Illinois, 60153
Marjorie Weinberg Cancer Center at Loyola-Gottlieb
Melrose Park, Illinois, 60160
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, 38120
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548
Saint Patrick Hospital - Community Hospital
Missoula, Montana, 59802
SSM Health Good Samaritan
Mount Vernon, Illinois, 62864
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, 37204
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Yale University
New Haven, Connecticut, 06520
Providence Newberg Medical Center
Newberg, Oregon, 97132
Henry Ford Medical Center-Columbus
Novi, Michigan, 48377
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Mercy Hospital Oklahoma City
Oklahoma City, Oklahoma, 73120
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Providence Willamette Falls Medical Center
Oregon City, Oregon, 97045
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Michigan Healthcare Professionals Pontiac
Pontiac, Michigan, 48341
Newland Medical Associates-Pontiac
Pontiac, Michigan, 48341
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341
Providence Portland Medical Center
Portland, Oregon, 97213
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Saint Charles Health System-Redmond
Redmond, Oregon, 97756
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
Mercy Clinic-Rolla-Cancer and Hematology
Rolla, Missouri, 65401
Phelps Health Delbert Day Cancer Institute
Rolla, Missouri, 65401
MyMichigan Medical Center Saginaw
Saginaw, Michigan, 48601
Oncology Hematology Associates of Saginaw Valley PC
Saginaw, Michigan, 48604
Heartland Regional Medical Center
Saint Joseph, Missouri, 64506
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Pacific Gynecology Specialists
Seattle, Washington, 98104
Swedish Medical Center-Ballard Campus
Seattle, Washington, 98107
Swedish Medical Center-Cherry Hill
Seattle, Washington, 98122-5711
Swedish Medical Center-First Hill
Seattle, Washington, 98122
PeaceHealth United General Medical Center
Sedro-Woolley, Washington, 98284
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, 29672
Henry Ford Macomb Health Center - Shelby Township
Shelby, Michigan, 48315
Providence Regional Cancer System-Shelton
Shelton, Washington, 98584
LSU Health Sciences Center at Shreveport
Shreveport, Louisiana, 71103
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi, 38671
Mercy Hospital Springfield
Springfield, Missouri, 65804
CoxHealth South Hospital
Springfield, Missouri, 65807
Mercy Infusion Center - Chippewa
St Louis, Missouri, 63109
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital South
St Louis, Missouri, 63128
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482
MyMichigan Medical Center Tawas
Tawas City, Michigan, 48764
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, 83301
PeaceHealth Southwest Medical Center
Vancouver, Washington, 98664
Providence Saint Mary Regional Cancer Center
Walla Walla, Washington, 99362
Mercy Hospital Washington
Washington, Missouri, 63090
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322
Saint Mary's Oncology/Hematology Associates of West Branch
West Branch, Michigan, 48661
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Henry Ford Wyandotte Hospital
Wyandotte, Michigan, 48192
Providence Regional Cancer System-Yelm
Yelm, Washington, 98597
Huron Gastroenterology PC
Ypsilanti, Michigan, 48106
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
Israel2 sites
Rambam Medical Center
Haifa, 31096
Shaare Zedek Medical Center
Jerusalem, 91031
Puerto Rico2 sites
Centro Comprensivo de Cancer de UPR
San Juan, 00927
San Juan City Hospital
San Juan, 00936
About this study
Official title: A Phase III Randomized Trial of Steroids + Tyrosine Kinase Inhibitor (TKI) Induction With Chemotherapy or Blinatumomab for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL) in Adults
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 ('BiTE') 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.
Read the detailed description
PRIMARY OBJECTIVE:
- To compare the overall survival (OS) following induction with steroids + TKI + blinatumomab versus induction with steroids + TKI + chemotherapy.
SECONDARY OBJECTIVES:
- To compare the rate of minimal residual disease (MRD) negative complete remission (CR) for patients treated with chemotherapy versus (vs) blinatumomab at the end of first induction (week 15).
II. To evaluate the rate of the MRD negative CR 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.
- 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 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 'chemoprotectant' 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 QD or ponatinib 30mg/day PO QD on days 1-21, methotrexate IV over 24 hours and IT on day 1, and cytarabine IV over 2 hours BID 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 BID 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 29 or 30.
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, followed by methotrexate IT on day 29 or 30.
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 every 3 months for first 2 years (from study registration), every 6 months for years 3-5, and then every 12 months for years 6-10.
- Being tested
- Biospecimen Collection, Blinatumomab, Bone Marrow Aspiration and Biopsy, Cyclophosphamide, Cytarabine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Correlative studies
BlinatumomabBiological
Also called AMG 103, AMG-103, AMG103, Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
Given IV
Bone Marrow Aspiration and BiopsyProcedure or surgery
Undergo bone marrow aspiration and biopsy
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518
Given IV
CytarabineDrug
Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
Given IV or IT
DasatinibDrug
Also called BMS 354825, BMS-354825, BMS354825, Dasatinib Hydrate
Given PO
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO or IV
Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin
Given IV
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
ElectrocardiographyProcedure or surgery
Also called ECG, EKG
Undergo ECG
Lumbar PunctureProcedure or surgery
Also called LP, Spinal Tap
Undergo lumbar puncture
MesnaDrug
Also called 2-Mercaptoethanesulfonate, Sodium Salt, Ausobronc, D-7093, Filesna
Given IV
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given IV or IT
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, MUGA
Undergo MUGA
Ponatinib HydrochlorideDrug
Also called AP24534 HCl, Iclusig
Given PO
PrednisoneDrug
Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl
Given PO
Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm A (steroid, TKI), Single Arm Pre-Induction | Active comparator | Patients receive prednisone PO QD on days 1-21 and ponatinib PO QD or dasatinib PO QD on days 1-21 based on investigator's choice. Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Dasatinib; Procedure: Echocardiography Test; Procedure: Electrocardiography; Procedure: Lumbar Puncture; Procedure: Multigated Acquisition Scan; Drug: Ponatinib Hydrochloride; Drug: Prednisone |
| Arm B (steroid, TKI, chemotherapy) | Experimental | See Detailed Description. Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dasatinib; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Electrocardiography; Procedure: Lumbar Puncture; Drug: Mesna; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Ponatinib Hydrochloride; Drug: Vincristine Sulfate |
| Arm C (steroid, TKI, chemotherapy, immunotherapy) | Experimental | 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 29 or 30.
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, followed by methotrexate IT on day 29 or 30.
Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Receives: Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Dasatinib; Drug: Dexamethasone; Procedure: Echocardiography Test; Procedure: Electrocardiography; Procedure: Lumbar Puncture; Drug: Mesna; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Ponatinib Hydrochloride |
| Arm D (steroid, TKI, chemotherapy, immunotherapy) | Experimental | 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.
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. Receives: Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Cyclophosphamide; Drug: Dasatinib; Drug: Dexamethasone; Procedure: Echocardiography Test; Procedure: Electrocardiography; Procedure: Lumbar Puncture; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Ponatinib Hydrochloride |
| Arm E (steroid, TKI, chemotherapy) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dasatinib; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Electrocardiography; Procedure: Lumbar Puncture; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Ponatinib Hydrochloride; Drug: Vincristine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
Will compare OS following induction with steroids + tyrosine kinase inhibitor (TKI) + blinatumomab and induction with steroids + TKI + chemotherapy. Will be based on an intent-to-treat analysis. Estimates of OS including medians and confidence intervals, will be calculated using the Kaplan-Meier method. Comparisons of OS between treatment arms will be conducted using the one-sided stratified log-rank test, stratified on the same factors used in the randomization. Cox proportional hazards models of OS, stratified on the same factors used in the randomization, will be used to assess the effect of treatment by adjusting other possible clinical and biological risk factors, including cytogenetic abnormalities.
Measured: Time between randomization and death from any cause, assessed up to 10 years from the date of registration
Secondary outcomes (4)
Rate of minimal residual disease (MRD) negative complete remission (CR)
Will be centrally evaluated. Will be compared between two arms using Fisher's exact test with a one-sided type I error rate of 2.5%. Multivariable logistic regression modeling will be used to adjust for other possible clinical and biological risk factors. For patients registered to Step 3 (re-induction), the rates of MRD negative CR and their corresponding 95% confidence intervals after re-induction will be given by treatment arm.
Measured: At the end of first induction (week 15)
Event free survival (EFS)
Will be based on an intent-to-treat analysis. Estimates of EFS including medians and confidence intervals, will be calculated using the Kaplan-Meier method. Comparisons of EFS between treatment arms will be conducted using the one-sided stratified log-rank test, stratified on the same factors used in the randomization. Cox proportional hazards models of EFS, stratified on the same factors used in the randomization, will be used to assess the effect of treatment by adjusting other possible clinical and biological risk factors, including cytogenetic abnormalities
Measured: Time from randomization to failure to achieve induction molecular remission by the end of first induction, confirmed molecular relapse after molecular remission or to death in remission, assessed up to 10 years from the date of registration
Rate of MRD negative CR
Will be centrally evaluated. Will be compared between two arms using Fisher's exact test with a one-sided type I error rate of 2.5%. Multivariable logistic regression modeling will be used to adjust for other possible clinical and biological risk factors. For patients registered to Step 3 (re-induction), the rates of MRD negative CR and their corresponding 95% confidence intervals after re-induction will be given by treatment arm.
Measured: After re-induction
Incidence of adverse events
All toxicity grades and reportable adverse events will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Measured: Up to 10 years from the date of registration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2020
- Study start25 Jan 2021
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 348 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Yishai Ofran, Principal investigator, ECOG-ACRIN Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04530565
- Sponsor's protocol ID
- NCI-2020-06381
- Other IDs
- NCI-2020-06381, EA9181, EA9181, U10CA180820
- Status last verified
- Aug 2026
- First submitted
- 27 Aug 2020
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
Publications
Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.
PubMed 41671463