Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma
Anaplastic Large Cell Lymphoma, ALK-Positive, Ann Arbor Stage II Noncutaneous Childhood Anaplastic Large Cell Lymphoma, Ann Arbor Stage III Noncutaneous Childhood Anaplastic Large Cell Lymphoma
About this trial
This is an interventional treatment trial for Anaplastic Large Cell Lymphoma, ALK-Positive
Eligibility Criteria
Inclusion Criteria:
- Newly diagnosed patients with histologically proven ALCL (International Classification of Diseases for Oncology [ICD-0] code: 9714/3)
- Disease must be cluster of differentiation (CD)30 positive
- Disease must be anaplastic lymphoma kinase (ALK) positive (defined by local institutional standards)
- Patients must have stage II, III, or IV disease
- Patients must have a life expectancy of >= 8 weeks
- Adequate Liver Function Defined As:
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for ALT is 45 U/L (within 7 days prior to enrollment)
- If the lab abnormality is thought to be due to the lymphoma the patient is eligible and dose adjustments should be made
- Adequate Cardiac Function Defined As:
- Shortening fraction of >= 27% by echocardiogram, or
- Ejection fraction of >= 50% by radionuclide angiogram
- Adequate Pulmonary Function Defined As:
- Patients with a history of pulmonary dysfunction must have no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry > 92% while breathing room air unless current dysfunction is due to the lymphoma in which case the patient is eligible
Exclusion Criteria:
- Patients with central nervous system (CNS) disease are not eligible
- Patients with disease limited to the skin are not eligible, regardless of how wide-spread
- Patients with stage I disease are not eligible
- Patients who have received any prior cytotoxic chemotherapy for the current diagnosis of ALCL or any cancer diagnosed previously are not eligible
- Previous steroid treatment and/or radiation treatment is not allowed unless it is for the emergent management of a mediastinal mass; emergent steroid treatment and/or radiation treatment should stop once protocol therapy is initiated
- Intrathecal chemotherapy prior to enrollment is allowed for the current diagnosis of ALCL as long as adequate cerebrospinal fluid (CSF) is obtained prior to administration of the intrathecal chemotherapy and subsequently demonstrated to be negative for ALCL
- Female patients who are pregnant are not eligible; pregnancy tests must be obtained in girls who are post menarchal
- Lactating females are not eligible unless they have agreed not to breastfeed their infants
- Sexually active patients of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of treatment and for 3 months after stopping treatment
- Patients with Down syndrome are not eligible due to the amount of methotrexate and potential for side effects
- Patients with an immunodeficiency that existed prior to diagnosis such as primary immunodeficiency syndromes or organ transplant recipients are not eligible
- Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates with narrow therapeutic indices: Patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use of these medications (if applicable) is allowed
- CYP3A4 inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed
- CYP3A4 inducers: patients chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, ritonavir, and St. John's wort are not eligible; the topical use of these medications (if applicable) is allowed
- Patients that are known to be positive for human immunodeficiency virus (HIV) are not eligible; note: inclusion of HIV positive patients will be considered at a later date
- Patients who weigh < 10 kg are not eligible
Sites / Locations
- Children's Hospital of Alabama
- Phoenix Childrens Hospital
- 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
- Valley Children's Hospital
- UCSF Benioff Children's Hospital 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
- Naval Medical Center -San Diego
- UCSF Medical Center-Parnassus
- UCSF Medical Center-Mission Bay
- 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
- Golisano Children's Hospital of Southwest Florida
- University of Florida Health Science Center - Gainesville
- Nemours Children's Clinic-Jacksonville
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Nicklaus Children's Hospital
- AdventHealth Orlando
- Arnold Palmer Hospital for Children
- Orlando Health Cancer Institute
- Nemours Children's Hospital
- 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
- Augusta University Medical Center
- Memorial Health University Medical Center
- University of Hawaii Cancer 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
- Advocate Children's Hospital-Oak Lawn
- Saint Jude Midwest Affiliate
- Southern Illinois University School of Medicine
- Riley Hospital for Children
- Ascension Saint Vincent Indianapolis Hospital
- Blank Children's Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- University of Kentucky/Markey Cancer Center
- Norton Children's Hospital
- Children's Hospital New Orleans
- Ochsner Medical Center Jefferson
- Maine Children's Cancer Program
- Sinai Hospital of Baltimore
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Massachusetts General Hospital Cancer Center
- Dana-Farber Cancer Institute
- Wayne State University/Karmanos Cancer Institute
- Ascension Saint John Hospital
- Michigan State University Clinical 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
- Columbia Regional
- 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
- University Medical Center of Southern Nevada
- 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
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Newark Beth Israel Medical Center
- Saint Joseph's Regional Medical Center
- University of New Mexico Cancer 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
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- NYP/Weill Cornell Medical Center
- University of Rochester
- 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
- Duke University Medical Center
- 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 - Muhlenberg
- Penn State Children's Hospital
- 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
- Prisma Health Richland Hospital
- BI-LO Charities Children's Cancer Center
- Sanford USD Medical Center - Sioux Falls
- T C Thompson Children's Hospital
- East Tennessee Childrens Hospital
- Saint Jude Children's Research 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
- Children's Hospital of San Antonio
- Methodist Children's Hospital of South Texas
- University of Texas Health Science Center at San Antonio
- Scott and White Memorial Hospital
- Primary Children's Hospital
- Inova Fairfax Hospital
- Children's Hospital of The King's Daughters
- Naval Medical Center - Portsmouth
- Virginia Commonwealth University/Massey Cancer Center
- Seattle Children's Hospital
- Providence Sacred Heart Medical Center and Children's Hospital
- Mary Bridge Children's Hospital and Health Center
- Madigan Army Medical Center
- University of Wisconsin Carbone Cancer Center
- Children's Hospital of Wisconsin
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm BV (brentuximab vedotin, combination chemotherapy)
Arm CZ (crizotinib, combination chemotherapy)
COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO BID or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5. COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5.
COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A. COURSE B (CYCLES 2, 4, AND 6): Patients receive crizotinib PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B.