Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
About this trial
This is an interventional treatment trial for B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
Eligibility Criteria
Inclusion Criteria:
- 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 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, 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 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])/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
Exclusion Criteria:
- 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
Sites / Locations
- University of Alabama at Birmingham Cancer CenterRecruiting
- Anchorage Associates in Radiation Medicine
- Anchorage Radiation Therapy Center
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Mercy Hospital Fort Smith
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Community Cancer InstituteRecruiting
- University Oncology Associates
- City of Hope Comprehensive Cancer CenterRecruiting
- UC San Diego Moores Cancer CenterRecruiting
- UC Irvine Health/Chao Family Comprehensive Cancer CenterRecruiting
- Yale University
- Augusta University Medical CenterRecruiting
- Hawaii Cancer Care - WestridgeRecruiting
- Pali Momi Medical CenterRecruiting
- Queen's Cancer Center - Pearlridge
- The Cancer Center of Hawaii-Pali Momi
- Hawaii Cancer Care Inc - Waterfront PlazaRecruiting
- Queen's Cancer Cenrer - POB I
- Queen's Medical Center
- Straub Clinic and HospitalRecruiting
- University of Hawaii Cancer Center
- Hawaii Cancer Care Inc-Liliha
- Kuakini Medical Center
- Queen's Cancer Center - Kuakini
- The Cancer Center of Hawaii-Liliha
- Kapiolani Medical Center for Women and Children
- Wilcox Memorial Hospital and Kauai Medical Clinic
- Saint Luke's Cancer Institute - BoiseRecruiting
- Saint Luke's Cancer Institute - Fruitland
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Saint Luke's Cancer Institute - Twin Falls
- Saint Anthony's Health
- Loyola Center for Health at Burr Ridge
- Northwestern UniversityRecruiting
- NorthShore University HealthSystem-Evanston HospitalRecruiting
- NorthShore University HealthSystem-Glenbrook HospitalRecruiting
- NorthShore University HealthSystem-Highland Park HospitalRecruiting
- Loyola Medicine Homer Glen
- Northwestern Medicine Lake Forest Hospital
- Loyola University Medical CenterRecruiting
- Marjorie Weinberg Cancer Center at Loyola-Gottlieb
- Good Samaritan Regional Health Center
- Mary Greeley Medical CenterRecruiting
- McFarland Clinic - AmesRecruiting
- McFarland Clinic - BooneRecruiting
- McFarland Clinic - Trinity Cancer CenterRecruiting
- McFarland Clinic - JeffersonRecruiting
- McFarland Clinic - MarshalltownRecruiting
- Central Care Cancer Center - Garden City
- Central Care Cancer Center - Great Bend
- University of Kansas Cancer CenterRecruiting
- University of Kansas Hospital-Indian Creek CampusRecruiting
- University of Kansas Hospital-Westwood Cancer CenterRecruiting
- The James Graham Brown Cancer Center at University of LouisvilleRecruiting
- LSU Health Sciences Center at Shreveport
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- Walter Reed National Military Medical CenterRecruiting
- Saint Joseph Mercy HospitalRecruiting
- Saint Joseph Mercy BrightonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - BrightonRecruiting
- Henry Ford Cancer Institute-Downriver
- Saint Joseph Mercy CantonRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - CantonRecruiting
- Saint Joseph Mercy ChelseaRecruiting
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea HospitalRecruiting
- Henry Ford Macomb Hospital-Clinton Township
- Henry Ford Medical Center-Fairlane
- Wayne State University/Karmanos Cancer InstituteRecruiting
- Henry Ford HospitalRecruiting
- Weisberg Cancer Treatment CenterRecruiting
- Genesee Cancer and Blood Disease Treatment CenterRecruiting
- Genesee Hematology Oncology PCRecruiting
- Genesys Hurley Cancer InstituteRecruiting
- Hurley Medical CenterRecruiting
- Allegiance Health
- Trinity Health Saint Mary Mercy Livonia HospitalRecruiting
- Henry Ford Medical Center-Columbus
- Henry Ford Macomb Health Center - Shelby Township
- Henry Ford West Bloomfield Hospital
- Huron Gastroenterology PCRecruiting
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor CampusRecruiting
- Mayo Clinic in Rochester
- Baptist Memorial Hospital and Cancer Center-DesotoRecruiting
- Saint Louis Cancer and Breast Institute-Ballwin
- Central Care Cancer Center - Bolivar
- Siteman Cancer Center at West County HospitalRecruiting
- Freeman Health SystemRecruiting
- Mercy Hospital Joplin
- Research Medical CenterRecruiting
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Heartland Regional Medical Center
- Saint Louis Cancer and Breast Institute-South City
- Washington University School of MedicineRecruiting
- Mercy Hospital South
- Siteman Cancer Center-South CountyRecruiting
- Siteman Cancer Center at Christian HospitalRecruiting
- Mercy Hospital Saint LouisRecruiting
- Siteman Cancer Center at Saint Peters HospitalRecruiting
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Mercy Hospital Washington
- Saint Patrick Hospital - Community Hospital
- Rutgers Cancer Institute of New Jersey
- Montefiore Medical Center - Moses CampusRecruiting
- University of RochesterRecruiting
- UNC Lineberger Comprehensive Cancer CenterRecruiting
- Duke University Medical CenterRecruiting
- Wake Forest University Health Sciences
- University of Cincinnati Cancer Center-UC Medical CenterRecruiting
- MetroHealth Medical CenterRecruiting
- Ohio State University Comprehensive Cancer CenterRecruiting
- University of Cincinnati Cancer Center-West ChesterRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Mercy Hospital Oklahoma City
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas ClinicRecruiting
- Bay Area Hospital
- Providence Newberg Medical CenterRecruiting
- Providence Willamette Falls Medical CenterRecruiting
- Providence Portland Medical CenterRecruiting
- Providence Saint Vincent Medical CenterRecruiting
- Saint Charles Health System-Redmond
- Lehigh Valley Hospital-Cedar CrestRecruiting
- Lehigh Valley Hospital - MuhlenbergRecruiting
- Geisinger Medical CenterRecruiting
- Pocono Medical CenterRecruiting
- University of Pennsylvania/Abramson Cancer CenterRecruiting
- Thomas Jefferson University HospitalRecruiting
- University of Pittsburgh Cancer Institute (UPCI)
- Geisinger Wyoming Valley/Henry Cancer CenterRecruiting
- Prisma Health Cancer Institute - SpartanburgRecruiting
- Medical University of South CarolinaRecruiting
- Prisma Health Cancer Institute - EasleyRecruiting
- Prisma Health Cancer Institute - ButternutRecruiting
- Prisma Health Cancer Institute - FarisRecruiting
- Prisma Health Greenville Memorial HospitalRecruiting
- Prisma Health Cancer Institute - EastsideRecruiting
- Prisma Health Cancer Institute - GreerRecruiting
- Prisma Health Cancer Institute - SenecaRecruiting
- Vanderbilt-Ingram Cancer Center Cool Springs
- Baptist Memorial Hospital and Cancer Center-MemphisRecruiting
- Vanderbilt Breast Center at One Hundred Oaks
- Vanderbilt University/Ingram Cancer CenterRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- Huntsman Cancer Institute/University of UtahRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- Providence Regional Cancer System-Aberdeen
- PeaceHealth Saint Joseph Medical Center
- Providence Regional Cancer System-Centralia
- Swedish Cancer Institute-Edmonds
- Providence Regional Cancer Partnership
- Swedish Cancer Institute-Issaquah
- Kadlec Clinic Hematology and OncologyRecruiting
- Providence Regional Cancer System-Lacey
- PeaceHealth Saint John Medical Center
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard Campus
- Swedish Medical Center-Cherry Hill
- Swedish Medical Center-First Hill
- PeaceHealth United General Medical Center
- Providence Regional Cancer System-Shelton
- PeaceHealth Southwest Medical Center
- Providence Saint Mary Regional Cancer Center
- Providence Regional Cancer System-Yelm
- Marshfield Medical Center-EC Cancer CenterRecruiting
- Gundersen Lutheran Medical CenterRecruiting
- University of Wisconsin Carbone Cancer CenterRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Medical College of WisconsinRecruiting
- Marshfield Clinic-Minocqua CenterRecruiting
- Marshfield Medical Center-Rice LakeRecruiting
- Marshfield Medical Center-River Region at Stevens PointRecruiting
- Marshfield Medical Center - WestonRecruiting
- Shaare Zedek Medical CenterRecruiting
- San Juan City HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Active Comparator
Experimental
Experimental
Experimental
Experimental
Arm A (steroid, TKI), Single Arm Pre-Induction
Arm B (steroid, TKI, chemotherapy)
Arm C (steroid, TKI, chemotherapy, immunotherapy)
Arm D (steroid, TKI, chemotherapy, immunotherapy)
Arm E (steroid, TKI, chemotherapy)
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.
See Detailed Description.
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.
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.
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.