Acute Lymphoblastic LeukemiaPhase 2NCT02143414
Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia
A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Blinatumomab in people with Acute Lymphoblastic Leukemia and B Acute Lymphoblastic Leukemia, run by National Cancer Institute (NCI) at 195 sites in United States.
Trial summary
This phase II trial studies the side effects and how well blinatumomab and combination chemotherapy or dasatinib, prednisone, and blinatumomab work in treating older patients with acute lymphoblastic leukemia. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Blinatumomab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 195 sitesUnited States
- Study dates
- 30 Jun 2015to 6 Jun 2027
- Phase
- Phase 2
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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Registration Step 1 - Induction/Re-Induction:
- Patients must have a new morphologic diagnosis of precursor B cell acute lymphoblastic leukemia (ALL) (non T cell) based on World Health Organization (WHO) criteria; patients with Burkitt's (L3) are excluded; patients with Ph-positive or Ph-like ALL with dasatinib-sensitive mutations or kinase fusions may have relapsed or refractory diagnoses
- NOTE: Relapsed/refractory Ph-positive patients or Ph-like patients with dasatinib-sensitive mutations or kinase fusions who have previous exposure to either dasatinib or another 2nd or 3rd generation tyrosine kinase inhibitor (TKI) will begin protocol therapy with Cohort 2: re-induction cycle 1
- Patients must have a diagnosis of Philadelphia chromosome negative ALL or Ph chromosome positive ALL by cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR); patients will be registered to receive treatment in either Cohort 1 (Ph-) or Cohort 2 (Ph+ or Ph-like DSMKF) based on these results; diagnostic specimens must be submitted to the site's local Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory and results of tests (cytogenetics, FISH or PCR) must confirm Ph status prior to registration; if not already known, breakpoint cluster region- abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) status (p190 or p210) must be evaluated in Ph-positive patients by PCR
- For Cohort 2, Ph-like testing is not required specifically for this study; however, to be registered to Cohort 2 under the Ph-like DSMKF criterion, the patient must have a known or presumed activating Ph-like signature and dasatinib-sensitive mutation or kinase fusion, such as: ABL1, ABL2, colony stimulating factor 1 receptor (CSF1R), platelet derived growth factor receptor beta (PDGFRB), platelet derived growth factor receptor alpha (PDGFRA), or fibroblast growth factor receptor (FGFR)s that was otherwise identified as part of normal standard of care; prior to registering any patients with a known or presumed activating Ph-like signature and dasatinib-sensitive mutations or kinase fusions (DSMKF) treating physicians must confirm eligibility with the study chairs via email; the study chairs must respond via email with confirmation of patient eligibility prior to patient registration
- All newly diagnosed patients must have evidence of ALL in their marrow or peripheral blood with at least 20% lymphoblasts present in blood or bone marrow collected within 28 days prior to registration; all relapsed/refractory patients (Cohort 2) must have at least 5% lymphoblasts present in blood or bone marrow collected within 28 days prior to registration; for relapsed/refractory patients, pathology and cytogenetics reports (both from time of original diagnosis) must be submitted at time of registration; if a bone marrow aspirate cannot be obtained despite an attempt (dry tap), appropriate immunohistochemistry (IHC) testing, including cluster of differentiation (CD)19, must be performed on the bone marrow biopsy to determine lineage; for ALL in marrow or peripheral blood, immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage (B cell, T cell or mixed B/T cell); appropriate marker studies including CD19 (B cell), must be performed; co-expression of myeloid antigens (CD13 and CD33) will not exclude patients; if possible, the lineage specific markers (myeloid cells) should be determined; the blood/bone marrow sample for these assays must be obtained within 28 days prior to registration; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible
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- Patient must not have a history or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, active ALL in the CNS confirmed by cerebrospinal fluid (CSF) analysis, or other significant CNS abnormalities
- Patients must have a lumbar puncture to determine CNS involvement of ALL within 14 days prior to registration; patients with CNS3 are excluded from the trial; patients with CNS1 or CNS2 will be eligible, but will be monitored for CNS involvement; note that intrathecal methotrexate administered during the pre-study lumbar puncture may count as the first dose of intrathecal therapy required as part of the study
- Cohort I, Ph-negative Patients Only: Patients must not have received any prior chemotherapy, radiation therapy, or other therapy for the treatment of ALL (other than those noted below) and must not be receiving any immunosuppressive therapy; patients may not have received any prior investigational therapy within 28 days prior to registration; patients must not have received any monoclonal antibody therapy within 42 days of registration; patients may have received the following within any time prior to registration: low dose chemotherapy-including: cyclophosphamide 1 g/m^2, oral 6-mercaptopurine, or oral methotrexate (other low dose chemotherapy may be allowable, however any other options not listed here should be confirmed with the study chairs), TKI therapy, steroids, hydroxyurea, leukapheresis, intrathecal chemotherapy or vincristine
- Cohort I, Ph-negative Patients Only: In the event that the patient's bone marrow blast count is >= 50% blasts, patients may be registered but should receive steroids for 3-5 days in order to reduce tumor burden prior to blinatumomab administration, as follows
- Prephase treatment with dexamethasone (10-20 mg/m^2) for 3-5 days is required for patients with bone marrow blasts >= 50%, peripheral blood blasts 15,000/uL or higher, or elevated lactate dehydrogenase (LDH) suggesting rapidly progressive disease per investigator opinion
- Pre-treatment should conclude at least 24 hours prior to the first dose of blinatumomab (although additional dexamethasone is automatically given as a pre-med prior to the first dose); at the time of first infusion of blinatumomab, the absolute peripheral blast count should be < 25,000/uL
- Note: For the purposes of the study, day 1 of the cycle will be the first day of blinatumomab administration
- Cohort I, Ph-negative Patients Only: It is preferred, but not required, that corticosteroids and hydroxyurea should start only after all diagnostic samples have been obtained; however, if the patient was previously on corticosteroids and/or hydroxyurea, this is allowable provided that the patient still has measurable disease at time of the bone marrow aspirate
- Corticosteroids and/or hydroxyurea, as well as any of the other therapies mentioned (with the exception of IV cyclophosphamide), may continue to be administered, at physician discretion, until 1 day prior to blinatumomab administration
- IV cyclophosphamide must be discontinued at least 7 days prior to blinatumomab administration
- Cohort 2, Ph-positive and Ph-like DSMKF Patients Only: Patients must NOT have received a prior autologous or allogeneic hematopoietic stem cell transplant at any time. Patients must NOT have received any chemotherapy, investigational agents, or undergone major surgery within 14 days prior to registration, with the following exceptions:
- Monoclonal antibodies must not have been received for 1 week prior to registration
- Chimeric antigen receptor (CAR) T-cells must not have been received for 28 days prior to registration
- Steroids, hydroxyurea, vincristine, 6-mercaptopurine, methotrexate, thioguanine and intrathecal chemotherapy are permitted within any timeframe prior to registration; Food and Drug Administration (FDA)-approved TKIs may also be administered until 1 day prior to start of study therapy (C1, D1); IV cyclophosphamide may be administered at doses of 1 g/m^2 or less until up to 7 days prior to registration
- Patients must be >= 65 years of age; for patients 65-69 years of age, patient must be deemed not suitable for standard intensive induction chemotherapy at the discretion of the local investigator, or must have refused standard intensive chemotherapy
- Cohort I, Ph-negative Patients Only: Patients must not be candidates for allogeneic hematopoietic stem cell transplant; NOTE: Subjects up to age 70 years who are considered fit for allogeneic hematopoietic stem cell transplant, should be considered for enrollment on E1910, in order to avoid competing with that study; if a patient is considered unfit for intensive chemotherapy at the time of initial diagnosis, but subsequently achieves a complete remission (CR), then it will be left to the treating physician's discretion to consider hematopoietic stem cell transplant (HSCT)
- Cohort I, Ph-negative Patients Only: Patients must have complete history and physical examination within 28 days prior to registration
- Cohort I, Ph-negative Patients Only: Patients must have a Zubrod performance status of 0-2
- Cohort I, Ph-negative Patients Only: Patients must have serum creatinine =< 1.5 mg/dl within 14 days prior to registration
- Cohort I, Ph-negative Patients Only: Patients must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (IULN) within 14 days prior to registration
- Cohort I, Ph-negative Patients Only: Patients must have total bilirubin =< 2.0 x IULN within 14 days prior to registration
- Cohort I, Ph-negative Patients Only: Patients must have alkaline phosphatase =< 2.5 x IULN within 14 days prior to registration
- Cohort I, Ph-negative Patients Only: Patients must not have systemic fungal, bacterial, viral or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
- Cohort I, Ph-negative Patients Only: Patients must not have Common Terminology Criteria for Adverse Events (CTCAE) >= grade 2 neuropathy (cranial, motor or sensory) within 14 days prior to registration
- Cohort I, Ph-negative Patients Only: Patients known to be positive for HIV (the human immunodeficiency virus) may be eligible, providing they meet the following additional criteria within 28 days prior to registration:
- No history of acquired immune deficiency syndrome (AIDS)-defining conditions
- CD4 cells > 350 cells/mm^3
- If on antiretroviral agents, must not include zidovudine or stavudine
- Viral load =< 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on combination antiretroviral therapy (cART) or =< 25,000 copies HIV mRNA/mm^3 if not on cART
- Highly active antiretroviral therapy (HAART) regimens are acceptable providing they have only weak P450A4 interactions
- Cohort I, Ph-negative Patients Only: Patients must not have any known autoimmune disease
- Cohort I, Ph-negative Patients Only: Patients must not have testicular involvement; if clinical or ultrasound findings are equivocal, biopsy must be performed; all tests for establishing testicular involvement must be completed within 14 days prior to registration
- Cohort I, Ph-negative Patients Only: Patients with evidence of extramedullary disease at diagnosis will have computed tomography (CT) scan or magnetic resonance imaging (MRI) of the chest, abdomen and pelvis to obtain baseline values within 28 days prior to registration
- Cohort I, Ph-negative Patients Only: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
- Cohort I, Ph-negative Patients Only: Patients must have the following tests within 28 days prior to registration to obtain baseline measurements:
- Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR)/fibrinogen (all patients)
- Cohort 1, Ph- Patients Only: Neurologic assessment
- Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must not have active pericardial effusion, ascites or pleural effusion of any grade based on chest x-ray and echocardiogram within 28 days prior to registration; exception: if the effusion is suspected to be related to the leukemia, the patient may have pericardial effusion =< grade 2 or pleural effusion =< grade 1
- Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must have ejection fraction >= 45% based on echocardiogram performed within 28 days prior to registration
- Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must have QTcF (by Fridericia calculation) < 480/msec based on electrocardiogram (EKG) performed within 28 days prior to registration
- Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must not be receiving any proton pump inhibitors at the time of registration
- Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 28 days prior to registration to S1318; specimens must be submitted to the site's preferred CLIA-approved cytogenetics laboratory; BCR-ABL status must be verified in Ph-positive patients by FISH, cytogenetics, and/or PCR prior to enrollment; if a patient is Ph-positive, PCR for both p190 and p210 must be sent
- Patients must be offered participation in specimen submission for future research; with patient's consent, specimens must be submitted as outlined
- Cohort 1, Ph-negative Patients Only: Patients must have specimens submitted for blinatumomab immunogenicity assessment; collection of pretreatment specimens must be completed within 28 days prior to registration to S1318; specimens must be submitted to LabConnect
- Cohort 2, Ph-positive and Ph-like DSMKF Patients Only: Patients must agree to have specimens submitted for blinatumomab immunogenicity testing if subsequently moved to a blinatumomab containing treatment regimen on protocol
- Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
- Registration Step 2 - Post-Remission Therapy:
- Cohort 1, Ph-negative Patients Only: Patients must have achieved CR or CRi within 2 cycles of induction/re-induction with blinatumomab
- NOTE: day 1 of post-remission = day 43 of the preceding cycle (+/- 3 days)
- Cohort 2, Ph-positive and Ph-like DSMKF Patients Only: Newly diagnosed Ph+, newly-diagnosed Ph-like DSMKF, and relapsed/refractory Ph+ patients without prior dasatinib or other 2nd or 3rd generation TKI therapy, must have achieved CR or CRi within 1 cycle of induction with dasatinib/prednisone, or within 2 cycles of re-induction with blinatumomab; relapsed/refractory Ph+ or Ph-like DSMKF patients with prior dasatinib or other 2nd or 3rd generation TKI therapy must have achieved CR or CRi within 2 cycles of re-induction therapy with blinatumomab
- NOTE: day 1 of post-remission = day 85 of the preceding induction cycle (+/- 3 days), or day 43 of the preceding re-induction cycle (+/- 3 days) as applicable
- Serum creatinine =< 1.5 mg/dl within 14 days prior to registration
- AST and ALT =< 3.0 x institutional upper limit of normal (IULN) within 14 days prior to registration
- Total bilirubin =< 2.0 x IULN within 14 days prior to registration
- Absolute neutrophil count (ANC) >= 750/mcL within 28 days prior to registration
- Platelets >= 50,000/mcL within 28 days prior to registration
- Patients must be registered to Step 2 within 28 days after count recovery; (Note: there is no maximum allotted time period for count recovery, providing patient remains in CR or CRi)
- All non-hematologic treatment related toxicities that are deemed clinically significant by the treating investigator must have resolved to =< grade 2
- Registration Step 3 - Maintenance: Patients must have documented CR or CRi within 28 days prior to registration; note that bone marrow examination is only required if there are clinical signs/symptoms of progression; if progression is a concern due to the length of the time for count recovery, a bone marrow examination is recommended
- Registration Step 3 - Maintenance: Patients must have serum creatinine =< 1.5 mg/dl within 14 days prior to registration
- Registration Step 3 - Maintenance: Patients must have AST and ALT =< 3.0 x institutional upper limit of normal (IULN) within 14 days prior to registration
- Registration Step 3 - Maintenance: Patients must have total bilirubin < 2.0 x institutional upper limit of normal (IULN) within 14 days prior to registration
- Registration Step 3 - Maintenance: Patients must have adequate marrow function as evidenced by ANC >= 750/mcL within 28 days prior to registration
- Registration Step 3 - Maintenance: Patients must have adequate marrow function as evidenced by platelets >= 75,000/mcL within 28 days prior to registration
- Registration Step 3 - Maintenance: All non-hematologic treatment related toxicities that are deemed clinically significant by the treating investigator must have resolved to =< grade 2
Who cannot join
None listed.
Trial locations and contacts
195 sites in 1 country.
195 sites in 1 country
United States195 sites
Hickman Cancer Center
Adrian, Michigan, 49221
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
McFarland Clinic - Ames
Ames, Iowa, 50010
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Northside Hospital
Atlanta, Georgia, 30342
Augusta University Medical Center
Augusta, Georgia, 30912
Rush-Copley Medical Center
Aurora, Illinois, 60504
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Bronson Battle Creek
Battle Creek, Michigan, 49017
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
OSF Saint Joseph Medical Center
Bloomington, Illinois, 61701
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Central Care Cancer Center - Bolivar
Bolivar, Missouri, 65613
Parkland Health Center-Bonne Terre
Bonne Terre, Missouri, 63628
McFarland Clinic - Boone
Boone, Iowa, 50036
Cox Cancer Center Branson
Branson, Missouri, 65616
Roswell Park Cancer Institute
Buffalo, New York, 14263
Illinois CancerCare-Canton
Canton, Illinois, 61520
Mercy Cancer Center - Cape Girardeau
Cape Girardeau, Missouri, 63703
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Memorial Hospital of Carbondale
Carbondale, Illinois, 62902
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Miami Valley Hospital South
Centerville, Ohio, 45459
Centralia Oncology Clinic
Centralia, Illinois, 62801
Cancer Center of Kansas - Chanute
Chanute, Kansas, 66720
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Oncology Hematology Care Inc-Eden Park
Cincinnati, Ohio, 45202
Oncology Hematology Care Inc-Mercy West
Cincinnati, Ohio, 45211
Oncology Hematology Care Inc-Anderson
Cincinnati, Ohio, 45230
Oncology Hematology Care Inc-Kenwood
Cincinnati, Ohio, 45236
Oncology Hematology Care Inc-Blue Ash
Cincinnati, Ohio, 45242
Case Western Reserve University
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Oncology Hematology Care Inc-Crestview
Crestview Hills, Kentucky, 41017
Baylor University Medical Center
Dallas, Texas, 75246
Carle at The Riverfront
Danville, Illinois, 61832
Good Samaritan Hospital - Dayton
Dayton, Ohio, 45406
Miami Valley Hospital
Dayton, Ohio, 45409
Miami Valley Hospital North
Dayton, Ohio, 45415
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Cancer Center of Kansas - Dodge City
Dodge City, Kansas, 67801
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
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
Cancer Center of Kansas - El Dorado
El Dorado, Kansas, 67042
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Oncology Hematology Care Inc-Healthplex
Fairfield, Ohio, 45014
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
Corewell Health Farmington Hills Hospital
Farmington Hills, Michigan, 48336
Blanchard Valley Hospital
Findlay, Ohio, 45840
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, 66701
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Western Illinois Cancer Treatment Center
Galesburg, Illinois, 61401
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303
Wayne Hospital
Greenville, Ohio, 45331
Greenville Health System Cancer Institute-Andrews
Greenville, South Carolina, 29601
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
William Beaumont Hospital-Grosse Pointe
Grosse Pointe, Michigan, 48230
Cancer Center of Kansas-Independence
Independence, Kansas, 67301
Franciscan Health Indianapolis
Indianapolis, Indiana, 46237
University of Mississippi Medical Center
Jackson, Mississippi, 39216
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129
MU Health Care Goldschmidt Cancer Center
Jefferson City, Missouri, 65109
Freeman Health System
Joplin, Missouri, 64804
Mercy Hospital Joplin
Joplin, Missouri, 64804
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Beacon Kalamazoo
Kalamazoo, Michigan, 49048
University of Kansas Cancer Center
Kansas City, Kansas, 66160
ECU Health Oncology Kenansville
Kenansville, North Carolina, 28349
Kettering Medical Center
Kettering, Ohio, 45429
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Cancer Center of Kansas-Kingman
Kingman, Kansas, 67068
ECU Health Oncology Kinston
Kinston, North Carolina, 28501
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
Cancer Center of Kansas-Liberal
Liberal, Kansas, 67905
John L McClellan Memorial Veterans Hospital
Little Rock, Arkansas, 72205
Loma Linda University Medical Center
Loma Linda, California, 92354
Los Angeles General Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
North Shore University Hospital
Manhasset, New York, 11030
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Toledo Clinic Cancer Centers-Maumee
Maumee, Ohio, 43537
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
Maumee, Ohio, 43537
Cancer Center of Kansas - McPherson
McPherson, Kansas, 67460
Franciscan Saint Anthony Health-Michigan City
Michigan City, Indiana, 46360
Woodland Cancer Care Center
Michigan City, Indiana, 46360
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Toledo Clinic Cancer Centers-Monroe
Monroe, Michigan, 48162
SSM Health Good Samaritan
Mount Vernon, Illinois, 62864
Trinity Health Muskegon Hospital
Muskegon, Michigan, 49444
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510
Yale University
New Haven, Connecticut, 06520
Long Island Jewish Medical Center
New Hyde Park, New York, 11040
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663
Cancer Center of Kansas - Newton
Newton, Kansas, 67114
Corewell Health Lakeland Hospitals - Niles Hospital
Niles, Michigan, 49120
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Nebraska Medicine-Village Pointe
Omaha, Nebraska, 68118
University of Nebraska Medical Center
Omaha, Nebraska, 68198
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Saint Charles Hospital
Oregon, Ohio, 43616
Orlando Health Cancer Institute
Orlando, Florida, 32806
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Radiation Oncology of Northern Illinois
Ottawa, Illinois, 61350
Cancer Center of Kansas - Parsons
Parsons, Kansas, 67357
Keck Medical Center of USC Pasadena
Pasadena, California, 91105
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
OSF Saint Francis Radiation Oncology at Pekin
Pekin, Illinois, 61554
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
Peoria, Illinois, 61615
Methodist Medical Center of Illinois
Peoria, Illinois, 61636
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Illinois CancerCare-Peru
Peru, Illinois, 61354
Valley Radiation Oncology
Peru, Illinois, 61354
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Providence Portland Medical Center
Portland, Oregon, 97213
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Cancer Center of Kansas - Pratt
Pratt, Kansas, 67124
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
Corewell Health Reed City Hospital
Reed City, Michigan, 49677
ECU Health Oncology Richlands
Richlands, North Carolina, 28574
Reid Health
Richmond, Indiana, 47374
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
Corewell Health William Beaumont University Hospital
Royal Oak, Michigan, 48073
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
Saint Joseph, Michigan, 49085
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, 63670
Cancer Center of Kansas - Salina
Salina, Kansas, 67401
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, 29672
LSU Health Sciences Center at Shreveport
Shreveport, Louisiana, 71103
Siouxland Regional Cancer Center
Sioux City, Iowa, 51101
Central Illinois Hematology Oncology Center
Springfield, Illinois, 62702
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Springfield Clinic
Springfield, Illinois, 62702
Springfield Memorial Hospital
Springfield, Illinois, 62781
Mercy Hospital Springfield
Springfield, Missouri, 65804
CoxHealth South Hospital
Springfield, Missouri, 65807
Springfield Regional Cancer Center
Springfield, Ohio, 45504
Springfield Regional Medical Center
Springfield, Ohio, 45504
Mercy Infusion Center - Chippewa
St Louis, Missouri, 63109
Missouri Baptist Medical Center
St Louis, Missouri, 63131
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, 63080
Mercy Health - Saint Anne Hospital
Toledo, Ohio, 43623
Toledo Clinic Cancer Centers-Toledo
Toledo, Ohio, 43623
Munson Medical Center
Traverse City, Michigan, 49684
Corewell Health Beaumont Troy Hospital
Troy, Michigan, 48085
Upper Valley Medical Center
Troy, Ohio, 45373
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719
Carle Cancer Center
Urbana, Illinois, 61801
The Carle Foundation Hospital
Urbana, Illinois, 61801
Cancer Center of Kansas - Wellington
Wellington, Kansas, 67152
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Associates In Womens Health
Wichita, Kansas, 67208
Cancer Center of Kansas-Wichita Medical Arts Tower
Wichita, Kansas, 67208
Ascension Via Christi Hospitals Wichita
Wichita, Kansas, 67214
Cancer Center of Kansas - Wichita
Wichita, Kansas, 67214
Wesley Medical Center
Wichita, Kansas, 67214
Cancer Center of Kansas - Winfield
Winfield, Kansas, 67156
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Wright-Patterson Medical Center
Wright-Patterson Air Force Base, Ohio, 45433
Rush-Copley Healthcare Center
Yorkville, Illinois, 60560
About this study
Official title: A Phase 2 Study of Blinatumomab and POMP (Prednisone, Vincristine, Methotrexate, 6-Mercaptopurine) for Patients >/= 65 Years of Age With Newly Diagnosed Philadelphia-Chromosome Negative (Ph-) Acute Lymphoblastic Leukemia (ALL) and of Dasatinib, Prednisone and Blinatumomab for Patients >/= 65 Years of Age With Newly Diagnosed Philadelphia-Chromosome Positive (Ph+) ALL, Relapsed/Refractory Ph+ ALL, and Philadelphia-Chromosome-Like Signature (Ph-Like) ALL (Newly Diagnosed or Relapsed/Refractory) With Known or Presumed Activating Dasatinib-Sensitive Mutations or Kinase Fusions (DSMKF)
This phase II trial studies the side effects and how well blinatumomab and combination chemotherapy or dasatinib, prednisone, and blinatumomab work in treating older patients with acute lymphoblastic leukemia. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as prednisone, vincristine sulfate, methotrexate, and mercaptopurine, 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. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab with combination chemotherapy or dasatinib and prednisone may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the 3-year survival rate in elderly patients with newly diagnosed Philadelphia (Ph)-negative acute lymphoblastic leukemia (ALL) treated with blinatumomab followed by POMP (prednisone, vincristine sulfate, methotrexate, and mercaptopurine) maintenance.
II. To evaluate in a preliminary manner (feasibility study) the safety of dasatinib-steroid based induction followed by blinatumomab treatment in combination with dasatinib followed by dasatinib-based maintenance in patients with newly diagnosed Ph-positive ALL, relapsed/refractory Ph-positive ALL, and Ph-like dasatinib-sensitive mutations or kinase fusions (DSMKF) ALL (newly-diagnosed relapsed or refractory).
SECONDARY OBJECTIVES:
- To evaluate toxicities in these patient populations treated with these regimens.
II. To estimate the rates of complete response (CR), complete remission with incomplete count recovery (CRi) and disease-free survival in Ph-negative patients.
III. To estimate disease-free and overall survival in Ph-positive ALL and Ph-like DSMKF ALL.
IV. To estimate in each cohort the rate of minimal residual disease (MRD) negativity, and the time to achieve MRD negativity (exploratory analysis).
- To determine whether anti-idiotype antibodies directed against blinatumomab develop with blinatumomab treatment in this study.
ADDITIONAL TRANSLATIONAL MEDICINE OBJECTIVES:
- To estimate the incidence of the Ph-like signature in elderly patients (>= 65 years of age) with newly diagnosed Philadelphia-chromosome negative ALL.
II. To estimate the incidence of the various tyrosine-kinase fusions, making up the Ph-like signature in elderly patients with newly diagnosed Philadelphia-chromosome negative ALL.
III. To evaluate outcomes (event free survival [EFS] and overall survival [OS]) in patients with the Ph-like signature versus those without the Ph-like signature in Ph-negative ALL.
IV. To describe via single cell transcriptomics the clonal diversity in gene expression of participants on the trial.
- To describe the methylation status of the overall genome as well as key driver genes of all participants in the trial.
OUTLINE: Patients are assigned to 1 of 2 treatment cohorts according to Philadelphia chromosome status.
COHORT I (PHILADELPHIA CHROMOSOME NEGATIVE PATIENTS):
INDUCTION: Patients receive blinatumomab intravenously (IV) continuously over 24 hours on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and echocardiography (ECHO) during screening and a computed tomography (CT) scan and/or magnetic resonance imaging (MRI) as well as blood sample collection and bone marrow aspiration and biopsy throughout the trial. Patients undergo a lumbar puncture during screening and on study. Patients may also undergo a biopsy during screening. (Closed to accrual 06/29/17)
RE-INDUCTION: Patients not achieving CR or CRi after Induction, receive blinatumomab IV continuously over 24 hours on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and ECHO during screening and a CT scan and/or MRI as well as blood sample collection and bone marrow aspiration and biopsy throughout the trial. Patients undergo a lumbar puncture during screening and on study. Patients may also undergo a biopsy during screening.
POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, lumbar puncture, and bone marrow aspiration and biopsy on study.
MAINTENANCE: Patients receive prednisone orally (PO) on days 1-5, vincristine sulfate IV on day 1, mercaptopurine PO on days 1-28, and methotrexate PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo a lumbar puncture and bone marrow aspiration and biopsy on study.
COHORT II (PHILADELPHIA CHROMOSOME POSITIVE PATIENTS):
INDUCTION: Patients receive dasatinib PO on days 1-84 and prednisone PO on days 1-24 with tapering on days 25-32 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and ECHO during screening and a CT scan and/or MRI throughout the trial. Patients undergo a lumbar puncture and bone marrow aspiration and biopsy during screening and on study. Patients may also undergo a biopsy during screening.
RE-INDUCTION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, a lumbar puncture, and bone marrow aspiration and biopsy on study.
POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28 and dasatinib PO on days 1-42. Treatment repeats every 42 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, lumbar puncture, and bone marrow aspiration and biopsy on study.
MAINTENANCE: Patients receive dasatinib PO on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive prednisone PO on days 1-5. Treatment repeats every 28 days for 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI as well as a lumbar puncture and bone marrow aspiration and biopsy on study.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually until 10 years from initial registration.
- Conditions
- Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, Recurrent Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia
- Being tested
- Biopsy Procedure, Biospecimen Collection, Blinatumomab, Bone Marrow Aspiration and Biopsy, Computed Tomography
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo a biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo a blood sample collection
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 a bone marrow aspiration and biopsy
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo a CT scan
DasatinibDrug
Also called BMS 354825, BMS-354825, BMS354825, Dasatinib Hydrate
Given PO
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
Lumbar PunctureProcedure or surgery
Also called LP, Spinal Tap
Undergo a lumbar puncture
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
MercaptopurineDrug
Also called 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine
Given PO
MethotrexateDrug
Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate
Given PO
Methotrexate SodiumDrug
Also called Sodium Methotrexate, Trexall, Xatmep
Given PO
PrednisoneDrug
Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl
Given PO
VincristineDrug
Also called LCR, Leurocristine, VCR, Vincrystine
Given IV
Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin
Given IV
X-Ray ImagingProcedure or surgery
Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs
Undergo an x-ray
| Study group | Role | What they receive |
|---|---|---|
| Cohort I (blinatumomab, POMP) | Experimental | See Detailed Description Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Methotrexate Sodium; Drug: Prednisone; Drug: Vincristine; Drug: Vincristine Sulfate; Procedure: X-Ray Imaging |
| Cohort II (dasatinib, prednisone, blinatumomab) | Experimental | See Detailed Description Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Computed Tomography; Drug: Dasatinib; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Prednisone; Procedure: X-Ray Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival Rate (Cohort I)
To evaluate the 3-year overall survival rate in elderly participants with newly diagnosed Ph-negative ALL treated with blinatumomab followed by POMP maintenance. Overall
Measured: From the day of registration on study until death from any cause, assessed at 3 years
Incidence of Dose-limiting Toxicity (Cohort II)
Defined as any grade 4 or higher treatment-related, non-hematologic toxicity in the first cycle of post-remission therapy (blinatumomab/dasatinib) graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Only participants with Ph-positive ALL or Ph-like DSMKF ALL were evaluated.
Measured: Up to day 42 of post-remission therapy
Secondary outcomes (7)
Number of Participants With Grade 3 Through 5 Adverse Events That Are Related to Study Drugs
Number of participants with Grade 3-5 adverse events that are possibly, probably or definitely related to study drug are reported by given type of adverse event. Adverse Events reported using CTCAE v 4.0, whereas Serious Adverse Events were reported with CTCAE v 5.0.
Measured: Duration of treatment and follow up until death or date of primary analysis (about 7.5 years)
Complete Response Rate (Cohort I)
Complete response rate is measured by the number of participants achieving complete remission (CR) or complete remission with incomplete platelet recovery (CRi) rate. CR is defined as having <5% marrow aspirate blasts, ANC >1,000/mcL, platelets > 100,000/mcL, no blasts in peripheral blood, and C1 extramedullary disease status. CRi is the same as CR but platelet count may be <= 100,000/mcL and/or ANC <=1,000/mcL.
Measured: Participants are assessed after induction treatment and again after re-induction treatment, if re-induction treatment is received (i.e. up to 85 days after registration)
Disease-free Survival (Cohort II)
An estimate of disease free survival in Ph-positive ALL and Ph-like DSMKF ALL (Cohort II). Disease free survival is measured by the number of years between the date the patient first achieves complete remission (CR) or complete remission with incomplete platelet recovery (CRi) until relapse from CR/CRi or death from any cause. CR is defined as having <5% marrow aspirate blasts, ANC >1,000/mcL, platelets > 100,000/mcL, no blasts in peripheral blood, and C1 extramedullary disease status. CRi is the same as CR but platelet count may be <= 100,000/mcL and/or ANC <=1,000/mcL.
Measured: Duration of treatment and follow up until death or date of primary analysis (about 7.5 years)
Overall Survival (Cohort II)
Estimated using the method of Kaplan-Meier.
Measured: Up to 10 years
Minimal Residual Disease Negativity
To estimate in each cohort the rate of minimal residual disease (MRD) negativity.
Measured: Participants are assessed after induction treatment and again after re-induction treatment, if re-induction treatment is received (i.e. up to 85 days after registration)
Time to Achieve Minimal Residual Disease Negativity
Will be examined separately in descriptive analyses within each cohort.
Measured: Up to 10 years
Anti-idiotype Antibody Development
To determine whether anti-idiotype antibodies directed against blinatumomab develop with blinatumomab treatment in this study.
Measured: Up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2014 (estimated)
- Study start30 Jun 2015
- Primary completion1 Jun 2022
- Study completion6 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Anjali S Advani, Principal investigator, SWOG Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02143414
- Sponsor's protocol ID
- NCI-2014-01047
- Other IDs
- NCI-2014-01047, SWOG-S1318, S1318, S1318, U10CA180888
- Status last verified
- Jun 2026
- First submitted
- 19 May 2014
- Last updated
- 4 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Advani AS, Moseley A, O'Dwyer KM, Wood BL, Park J, Wieduwilt M, Jeyakumar D, Yaghmour G, Atallah EL, Gerds AT, O'Brien SM, Liesveld JL, Othus M, Litzow M, Stone RM, Sharon E, Erba HP. Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph+ acute lymphoblastic leukemia. Blood Adv. 2023 Apr 11;7(7):1279-1285. doi: 10.1182/bloodadvances.2022008216.
PubMed 36322825