Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
Recurrent B Acute Lymphoblastic Leukemia
About this trial
This is an interventional treatment trial for Recurrent B Acute Lymphoblastic Leukemia
Eligibility Criteria
Inclusion Criteria:
- First relapse of B-ALL, allowable sites of disease include isolated bone marrow, combined bone marrow and CNS and/or testicular, and isolated CNS and/or testicular; extramedullary sites are limited to the CNS and testicles
- No waiting period for patients who relapse while receiving standard maintenance therapy
- Patients who relapse on frontline therapy in phases other than maintenance must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Cytotoxic therapy: at least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy, or maintenance chemotherapy, or intrathecal chemotherapy (methotrexate strongly preferred) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status
- Biologic (anti-neoplastic) agent: at least 7 days since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
- Stem cell transplant or rescue: patient has not had a prior stem cell transplant or rescue
- Patient has not had prior treatment with blinatumomab
- With the exception of intrathecal chemotherapy (methotrexate strongly preferred; cytarabine is permissible) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status, patient has not received prior relapse-directed therapy (i.e., this protocol is intended as the INITIAL treatment of first relapse)
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- 1 to < 2 years: =< 0.6 mg/dL
- 2 to < 6 years: =< 0.8 mg/dL
- 6 to < 10 years: =< 1 mg/dL
- 10 to < 13 years: =< 1.2 mg/dL
- 13 to < 16 years: =< 1.5 mg/dL (males) and =< 1.4 mg/dL (females)
- >= 16 years: =< 1.7 mg/dL (males) and =< 1.4 mg/dL (females)
- Direct bilirubin < 3.0 mg/dL
- Shortening fraction of >= 27% by echocardiogram, or
- Ejection fraction of >= 50% by radionuclide angiogram
- All patients and/or their parent or legal guardian must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
- Patients with Philadelphia chromosome positive/breakpoint cluster region protein (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL are not eligible
- Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia are not eligible
- Patients with T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL) are not eligible
- Patients with B-lymphoblastic lymphoma (B-LL) are not eligible
- Patients with known optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
- Patients known to have one of the following concomitant genetic syndromes: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
- Patients with known human immunodeficiency virus (HIV) infection
- Patients with known allergy to mitoxantrone, cytarabine, or both etoposide and etoposide phosphate (Etopophos)
- Lactating females who plan to breastfeed
- Patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
- Patients with pre-existing significant central nervous system pathology that would preclude treatment with blinatumomab, including: history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder, or autoimmune disease with CNS involvement are not eligible; patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible; (patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved)
- Patients with uncontrolled seizure disorder are not eligible; (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs remain eligible)
Sites / Locations
- Children's Hospital of Alabama
- USA Health Strada Patient Care Center
- Providence Alaska Medical Center
- Banner Children's at Desert
- Phoenix Childrens Hospital
- Banner University Medical Center - Tucson
- Arkansas Children's Hospital
- Kaiser Permanente Downey Medical Center
- City of Hope Comprehensive Cancer Center
- Loma Linda University Medical Center
- Miller Children's and Women's Hospital Long Beach
- Children's Hospital Los Angeles
- Cedars Sinai Medical Center
- Mattel Children's Hospital UCLA
- Valley Children's Hospital
- UCSF Benioff Children's Hospital Oakland
- Kaiser Permanente-Oakland
- Children's Hospital of Orange County
- Lucile Packard Children's Hospital Stanford University
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Rady Children's Hospital - San Diego
- UCSF Medical Center-Mission Bay
- Santa Barbara Cottage Hospital
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Children's Hospital Colorado
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
- Connecticut Children's Medical Center
- Yale University
- Alfred I duPont Hospital for Children
- Children's National Medical Center
- Broward Health Medical Center
- Golisano Children's Hospital of Southwest Florida
- University of Florida Health Science Center - Gainesville
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Nemours Children's Clinic-Jacksonville
- Palms West Radiation Therapy
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- AdventHealth Orlando
- Arnold Palmer Hospital for Children
- Nemours Children's Clinic - Pensacola
- Johns Hopkins All Children's Hospital
- Tampa General Hospital
- Saint Joseph's Hospital/Children's Hospital-Tampa
- Saint Mary's Hospital
- Children's Healthcare of Atlanta - Egleston
- Memorial Health University Medical Center
- Kapiolani Medical Center for Women and Children
- Saint Luke's Cancer Institute - Boise
- Lurie Children's Hospital-Chicago
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Loyola University Medical Center
- Advocate Children's Hospital-Oak Lawn
- Advocate Children's Hospital-Park Ridge
- Saint Jude Midwest Affiliate
- Southern Illinois University School of Medicine
- Riley Hospital for Children
- Ascension Saint Vincent Indianapolis Hospital
- University of Kentucky/Markey Cancer Center
- Norton Children's Hospital
- Ochsner Medical Center Jefferson
- Eastern Maine Medical Center
- Maine Children's Cancer Program
- University of Maryland/Greenebaum Cancer Center
- Sinai Hospital of Baltimore
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- Tufts Children's Hospital
- Baystate Medical Center
- UMass Memorial Medical Center - University Campus
- C S Mott Children's Hospital
- Wayne State University/Karmanos Cancer Institute
- Ascension Saint John Hospital
- Michigan State University Clinical Center
- Hurley Medical Center
- Helen DeVos Children's Hospital at Spectrum Health
- Beaumont Children's Hospital-Royal Oak
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- University of Mississippi Medical Center
- Children's Mercy Hospitals and Clinics
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Children's Hospital and Medical Center of Omaha
- University of Nebraska Medical Center
- Sunrise Hospital and Medical Center
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Summerlin Hospital Medical Center
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Hackensack University Medical Center
- Morristown Medical Center
- Saint Peter's University Hospital
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Newark Beth Israel Medical Center
- Saint Joseph's Regional Medical Center
- Albany Medical Center
- Montefiore Medical Center - Moses Campus
- Roswell Park Cancer Institute
- NYU Winthrop Hospital
- The Steven and Alexandra Cohen Children's Medical Center of New York
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai Hospital
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- NYP/Weill Cornell Medical Center
- University of Rochester
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- New York Medical College
- Mission Hospital
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Novant Health Presbyterian Medical Center
- Duke University Medical Center
- East Carolina University
- Wake Forest University Health Sciences
- Children's Hospital Medical Center of Akron
- Cincinnati Children's Hospital Medical Center
- Rainbow Babies and Childrens Hospital
- Cleveland Clinic Foundation
- Nationwide Children's Hospital
- Dayton Children's Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- University of Oklahoma Health Sciences Center
- Legacy Emanuel Children's Hospital
- Oregon Health and Science University
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- Geisinger Medical Center
- Children's Hospital of Philadelphia
- Saint Christopher's Hospital for Children
- Children's Hospital of Pittsburgh of UPMC
- Rhode Island Hospital
- Medical University of South Carolina
- BI-LO Charities Children's Cancer Center
- Sanford USD Medical Center - Sioux Falls
- T C Thompson Children's Hospital
- East Tennessee Childrens Hospital
- The Children's Hospital at TriStar Centennial
- Vanderbilt University/Ingram Cancer Center
- Dell Children's Medical Center of Central Texas
- Driscoll Children's Hospital
- Medical City Dallas Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- El Paso Children's Hospital
- Cook Children's Medical Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- Covenant Children's Hospital
- Children's Hospital of San Antonio
- Methodist Children's Hospital of South Texas
- Scott and White Memorial Hospital
- Primary Children's Hospital
- University of Virginia Cancer Center
- Inova Fairfax Hospital
- Children's Hospital of The King's Daughters
- Virginia Commonwealth University/Massey Cancer Center
- Carilion Children's
- Seattle Children's Hospital
- Providence Sacred Heart Medical Center and Children's Hospital
- Madigan Army Medical Center
- West Virginia University Charleston Division
- West Virginia University Healthcare
- Saint Vincent Hospital Cancer Center Green Bay
- Marshfield Medical Center-Marshfield
- Children's Hospital of Wisconsin
- Princess Margaret Hospital for Children
- Perth Children's Hospital
- British Columbia Children's Hospital
- CancerCare Manitoba
- Janeway Child Health Centre
- IWK Health Centre
- McMaster Children's Hospital at Hamilton Health Sciences
- Kingston Health Sciences Centre
- Children's Hospital
- Children's Hospital of Eastern Ontario
- Hospital for Sick Children
- The Montreal Children's Hospital of the MUHC
- Centre Hospitalier Universitaire Sainte-Justine
- Saskatoon Cancer Centre
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
- Starship Children's Hospital
- Christchurch Hospital
- HIMA San Pablo Oncologic Hospital
- San Jorge Children's Hospital
- University Pediatric Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Experimental
Active Comparator
Experimental
Arm A (HR and IR control)
Arm B (HR and IR blinatumomab)
Arm C (LR control)
Arm D (LR blinatumomab)
Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT. Closed effective September 18, 2019.
Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT.
Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance.
Patients receive Block 2 over 4 weeks, Blinatumomab Cycle 1 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Cycle 2 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Cycle 3 over 5 weeks, and then Maintenance.