The following info and data is provided "as is" to help patients around the globe.
We do not endorse or review these studies in any way.
Brief Title: Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
Official Title: Risk-Stratified Randomized Phase III Testing of Blinatumomab (NSC#765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)
Study ID: NCT02101853
Brief Summary: This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab may allow the body's immune system to attack and destroy some types of leukemia cells. It is not yet known whether blinatumomab is more effective than standard combination chemotherapy in treating relapsed B-cell acute lymphoblastic leukemia.
Detailed Description: PRIMARY OBJECTIVES: I. To compare disease free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapse B-cell acute lymphoblastic leukemia (B-ALL) patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization) as a part of a treatment regimen prior to allogeneic bone marrow transplantation. (Closed to enrollment effective September 18, 2019) II. To compare the DFS of low risk (LR) relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization). (Closed to enrollment effective September 30, 2019) SECONDARY OBJECTIVES: I. To compare overall survival (OS) of HR and IR relapse B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization). (Closed to enrollment effective September 18, 2019) II. To compare OS of LR relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization). EXPLORATORY OBJECTIVES: I. To compare the rates of minimal residual disease (MRD) \>= 0.01% at the end of block 2 and block 3 for HR and IR relapse B-ALL patients in HR/IR randomization. II. To estimate, for treatment failure (TF) patients not previously receiving blinatumomab, the hematologic complete remission rate (CR), rate of MRD \< 0.01%, and proportion able to proceed to hematopoietic stem cell transplant (HSCT) in CR after treatment with blinatumomab. III. To assess the feasibility and safety of rapid taper of immune suppression for the subset of HSCT patients with MRD \>= 0.01% pre- and/or post-HSCT with no acute graft versus host disease (aGVHD). IV. To evaluate blinatumomab pharmacokinetics (PK) and explore exposure-response relationships for measures of safety and effectiveness. OUTLINE: All patients receive Block 1 over 4 weeks. BLOCK 1: Patients receive dexamethasone orally (PO) twice daily (BID) or intravenously (IV) on days 1-5 and 15-19; vincristine sulfate IV over 1 minute on days 1, 8, 15, and 22; pegaspargase IV over 1-2 hours on days 3 and 17; mitoxantrone hydrochloride IV over 15-30 minutes on days 1-2, and methotrexate intrathecally (IT) on day 1. Patients with central nervous system (CNS) 1 or CNS2 also receive methotrexate IT on day 8. Patients with CNS3 (including isolated CNS relapse) also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8, 15, and 22. High risk and intermediate risk patients are then assigned to randomization R1. Low risk patients are assigned to randomization R2. RANDOMIZATION R1 (HR and IR patients): Patients are randomized to 1 of 2 treatment arms. Effective 09/18/2019, HR/IR patients not yet randomized are not eligible for post-Induction therapy on AALL1331 and will be removed from protocol therapy. Patients receiving therapy on Arm A prior to Amendment #10A who have not yet received day 22 treatment on Block 3 will be offered the opportunity to cross over to Arm B to receive blinatumomab. ARM A: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT if eligible. Patients with persistent testicular involvement after Block 1 receive testicular radiation during the Block 2. ARM B: Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT if eligible. Patients with persistent testicular involvement after Block 1 receive testicular radiation during the first block of blinatumomab. RANDOMIZATION R2 (LR patients): LR patients are randomized to 1 of 2 treatment arms. ARM C: 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. CNS3 patients receive chemoradiation post-Maintenance Cycle 1. Patients with persistent testicular involvement after Block 1 receive testicular radiation during Block 2. ARM D: 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. CNS3 patients receive chemoradiation post Maintenance Cycle 1. Patients with persistent testicular involvement after Block 1 receive testicular radiation during Block 2. BLOCK 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; methotrexate IV over 36 hours on day 8; leucovorin calcium IV or PO on days 10-11; pegaspargase IV over 1-2 hours on day 9 or 10; cyclophosphamide IV over 15-30 minutes on days 15-19; and etoposide IV over 1-2 hours on days 15-19. Patients with CNS1 or CNS2 also receive methotrexate IT on day 8. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 22. BLOCK 3: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9; asparaginase intramuscularly (IM) or IV over 1 hour on days 2, 4, 9, 11, and 23; methotrexate IT on day 1and IV over 36 hours on day 22; leucovorin calcium PO or IV on days 24-25. Patients with CNS1 or CNS2 also receive methotrexate IT on day 22. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 22. BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28. Patients with CNS1 or CNS2 also receive methotrexate IT on days 15 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 15 and 29. BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV continuously on days 1-28. Patients with CNS1 or CNS2 also receive methotrexate IT on days 8 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 29. BLINATUMOMAB BLOCK 3: Patients receive blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV on day 1. CONTINUATION 1 \& 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; mercaptopurine tablet PO on days 1-42; methotrexate PO on days 8, 15, 29, and 36; or; cyclophosphamide IV over 15-30 minutes on days 43 and 50; etoposide IV over 1-2 hours on days 43 and 50; thioguanine PO once daily on days 43-49; and cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 44-47 and 51-54. Patients with CNS1 or CNS2 also receive methotrexate IT on days 1 and 43, methotrexate PO every 6 hours for 4 doses on day 22, leucovorin calcium PO every 6 hours for 2 doses on day 24. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1 and 43 ; methotrexate IV over 36 hours on day 22; and leucovorin calcium IV or PO every 6 hours on days 24-25. MAINTENANCE: Patients receive dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; vincristine sulfate IV over 1 minute on days 1, 29, and 57; mercaptopurine tablet PO on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Patients with CNS1 or CNS2 also receive methotrexate IT on day 1. Patients with CNS3 receive Triple Intrathecal Therapy (ITT) on day 1. Cycles repeat every 12 weeks for up to 2 years from the beginning of treatment in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMORADIATION (LR CNS3 PATIENTS ONLY): Following maintenance cycle 1, patients receive 1800 cGy cranial radiation; dexamethasone PO BID or IV on days 1-7 and 15-21; vincristine sulfate IV over 1 minute on days 1, 8 and 15; and pegaspargase IV over 1-2 hours on day 1. Patients then resume maintenance with cycle 2 and beyond. After completion of study treatment, patients are followed up annually for 10 years.
Minimum Age: 1 Year
Eligible Ages: CHILD, ADULT
Sex: ALL
Healthy Volunteers: No
Children's Hospital of Alabama, Birmingham, Alabama, United States
USA Health Strada Patient Care Center, Mobile, Alabama, United States
Providence Alaska Medical Center, Anchorage, Alaska, United States
Banner Children's at Desert, Mesa, Arizona, United States
Phoenix Childrens Hospital, Phoenix, Arizona, United States
Banner University Medical Center - Tucson, Tucson, Arizona, United States
Arkansas Children's Hospital, Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center, Downey, California, United States
City of Hope Comprehensive Cancer Center, Duarte, California, United States
Loma Linda University Medical Center, Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach, Long Beach, California, United States
Children's Hospital Los Angeles, Los Angeles, California, United States
Cedars Sinai Medical Center, Los Angeles, California, United States
Mattel Children's Hospital UCLA, Los Angeles, California, United States
Valley Children's Hospital, Madera, California, United States
UCSF Benioff Children's Hospital Oakland, Oakland, California, United States
Kaiser Permanente-Oakland, Oakland, California, United States
Children's Hospital of Orange County, Orange, California, United States
Lucile Packard Children's Hospital Stanford University, Palo Alto, California, United States
Sutter Medical Center Sacramento, Sacramento, California, United States
University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
Rady Children's Hospital - San Diego, San Diego, California, United States
UCSF Medical Center-Mission Bay, San Francisco, California, United States
Santa Barbara Cottage Hospital, Santa Barbara, California, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, United States
Children's Hospital Colorado, Aurora, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center, Denver, Colorado, United States
Connecticut Children's Medical Center, Hartford, Connecticut, United States
Yale University, New Haven, Connecticut, United States
Alfred I duPont Hospital for Children, Wilmington, Delaware, United States
Children's National Medical Center, Washington, District of Columbia, United States
Broward Health Medical Center, Fort Lauderdale, Florida, United States
Golisano Children's Hospital of Southwest Florida, Fort Myers, Florida, United States
University of Florida Health Science Center - Gainesville, Gainesville, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital, Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville, Jacksonville, Florida, United States
Palms West Radiation Therapy, Loxahatchee Groves, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami, Florida, United States
AdventHealth Orlando, Orlando, Florida, United States
Arnold Palmer Hospital for Children, Orlando, Florida, United States
Nemours Children's Clinic - Pensacola, Pensacola, Florida, United States
Johns Hopkins All Children's Hospital, Saint Petersburg, Florida, United States
Tampa General Hospital, Tampa, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa, Tampa, Florida, United States
Saint Mary's Hospital, West Palm Beach, Florida, United States
Children's Healthcare of Atlanta - Egleston, Atlanta, Georgia, United States
Memorial Health University Medical Center, Savannah, Georgia, United States
Kapiolani Medical Center for Women and Children, Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise, Boise, Idaho, United States
Lurie Children's Hospital-Chicago, Chicago, Illinois, United States
University of Illinois, Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center, Chicago, Illinois, United States
Loyola University Medical Center, Maywood, Illinois, United States
Advocate Children's Hospital-Oak Lawn, Oak Lawn, Illinois, United States
Advocate Children's Hospital-Park Ridge, Park Ridge, Illinois, United States
Saint Jude Midwest Affiliate, Peoria, Illinois, United States
Southern Illinois University School of Medicine, Springfield, Illinois, United States
Riley Hospital for Children, Indianapolis, Indiana, United States
Ascension Saint Vincent Indianapolis Hospital, Indianapolis, Indiana, United States
University of Kentucky/Markey Cancer Center, Lexington, Kentucky, United States
Norton Children's Hospital, Louisville, Kentucky, United States
Ochsner Medical Center Jefferson, New Orleans, Louisiana, United States
Eastern Maine Medical Center, Bangor, Maine, United States
Maine Children's Cancer Program, Scarborough, Maine, United States
University of Maryland/Greenebaum Cancer Center, Baltimore, Maryland, United States
Sinai Hospital of Baltimore, Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland, United States
Walter Reed National Military Medical Center, Bethesda, Maryland, United States
Tufts Children's Hospital, Boston, Massachusetts, United States
Baystate Medical Center, Springfield, Massachusetts, United States
UMass Memorial Medical Center - University Campus, Worcester, Massachusetts, United States
C S Mott Children's Hospital, Ann Arbor, Michigan, United States
Wayne State University/Karmanos Cancer Institute, Detroit, Michigan, United States
Ascension Saint John Hospital, Detroit, Michigan, United States
Michigan State University Clinical Center, East Lansing, Michigan, United States
Hurley Medical Center, Flint, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health, Grand Rapids, Michigan, United States
Beaumont Children's Hospital-Royal Oak, Royal Oak, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis, Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center, Minneapolis, Minnesota, United States
Mayo Clinic in Rochester, Rochester, Minnesota, United States
University of Mississippi Medical Center, Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics, Kansas City, Missouri, United States
Washington University School of Medicine, Saint Louis, Missouri, United States
Mercy Hospital Saint Louis, Saint Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha, Omaha, Nebraska, United States
University of Nebraska Medical Center, Omaha, Nebraska, United States
Sunrise Hospital and Medical Center, Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation, Las Vegas, Nevada, United States
Summerlin Hospital Medical Center, Las Vegas, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center, Lebanon, New Hampshire, United States
Hackensack University Medical Center, Hackensack, New Jersey, United States
Morristown Medical Center, Morristown, New Jersey, United States
Saint Peter's University Hospital, New Brunswick, New Jersey, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital, New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center, Newark, New Jersey, United States
Saint Joseph's Regional Medical Center, Paterson, New Jersey, United States
Albany Medical Center, Albany, New York, United States
Montefiore Medical Center - Moses Campus, Bronx, New York, United States
Roswell Park Cancer Institute, Buffalo, New York, United States
NYU Winthrop Hospital, Mineola, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York, New York, United States
Mount Sinai Hospital, New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York, New York, United States
NYP/Weill Cornell Medical Center, New York, New York, United States
University of Rochester, Rochester, New York, United States
Stony Brook University Medical Center, Stony Brook, New York, United States
State University of New York Upstate Medical University, Syracuse, New York, United States
New York Medical College, Valhalla, New York, United States
Mission Hospital, Asheville, North Carolina, United States
UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute, Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center, Charlotte, North Carolina, United States
Duke University Medical Center, Durham, North Carolina, United States
East Carolina University, Greenville, North Carolina, United States
Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States
Children's Hospital Medical Center of Akron, Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Rainbow Babies and Childrens Hospital, Cleveland, Ohio, United States
Cleveland Clinic Foundation, Cleveland, Ohio, United States
Nationwide Children's Hospital, Columbus, Ohio, United States
Dayton Children's Hospital, Dayton, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital, Toledo, Ohio, United States
University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
Legacy Emanuel Children's Hospital, Portland, Oregon, United States
Oregon Health and Science University, Portland, Oregon, United States
Lehigh Valley Hospital-Cedar Crest, Allentown, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg, Bethlehem, Pennsylvania, United States
Geisinger Medical Center, Danville, Pennsylvania, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
Saint Christopher's Hospital for Children, Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States
Rhode Island Hospital, Providence, Rhode Island, United States
Medical University of South Carolina, Charleston, South Carolina, United States
BI-LO Charities Children's Cancer Center, Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls, Sioux Falls, South Dakota, United States
T C Thompson Children's Hospital, Chattanooga, Tennessee, United States
East Tennessee Childrens Hospital, Knoxville, Tennessee, United States
The Children's Hospital at TriStar Centennial, Nashville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center, Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas, Austin, Texas, United States
Driscoll Children's Hospital, Corpus Christi, Texas, United States
Medical City Dallas Hospital, Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas, Dallas, Texas, United States
El Paso Children's Hospital, El Paso, Texas, United States
Cook Children's Medical Center, Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center, Houston, Texas, United States
Covenant Children's Hospital, Lubbock, Texas, United States
Children's Hospital of San Antonio, San Antonio, Texas, United States
Methodist Children's Hospital of South Texas, San Antonio, Texas, United States
Scott and White Memorial Hospital, Temple, Texas, United States
Primary Children's Hospital, Salt Lake City, Utah, United States
University of Virginia Cancer Center, Charlottesville, Virginia, United States
Inova Fairfax Hospital, Falls Church, Virginia, United States
Children's Hospital of The King's Daughters, Norfolk, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center, Richmond, Virginia, United States
Carilion Children's, Roanoke, Virginia, United States
Seattle Children's Hospital, Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital, Spokane, Washington, United States
Madigan Army Medical Center, Tacoma, Washington, United States
West Virginia University Charleston Division, Charleston, West Virginia, United States
West Virginia University Healthcare, Morgantown, West Virginia, United States
Saint Vincent Hospital Cancer Center Green Bay, Green Bay, Wisconsin, United States
Marshfield Medical Center-Marshfield, Marshfield, Wisconsin, United States
Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
Princess Margaret Hospital for Children, Perth, Western Australia, Australia
Perth Children's Hospital, Perth, Western Australia, Australia
British Columbia Children's Hospital, Vancouver, British Columbia, Canada
CancerCare Manitoba, Winnipeg, Manitoba, Canada
Janeway Child Health Centre, Saint John's, Newfoundland and Labrador, Canada
IWK Health Centre, Halifax, Nova Scotia, Canada
McMaster Children's Hospital at Hamilton Health Sciences, Hamilton, Ontario, Canada
Kingston Health Sciences Centre, Kingston, Ontario, Canada
Children's Hospital, London, Ontario, Canada
Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
Hospital for Sick Children, Toronto, Ontario, Canada
The Montreal Children's Hospital of the MUHC, Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
Saskatoon Cancer Centre, Saskatoon, Saskatchewan, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL), Quebec, , Canada
Starship Children's Hospital, Grafton, Auckland, New Zealand
Christchurch Hospital, Christchurch, , New Zealand
HIMA San Pablo Oncologic Hospital, Caguas, , Puerto Rico
San Jorge Children's Hospital, San Juan, , Puerto Rico
University Pediatric Hospital, San Juan, , Puerto Rico
Name: Patrick A Brown
Affiliation: Children's Oncology Group
Role: PRINCIPAL_INVESTIGATOR