Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma
NCT ID: NCT01979536
Last Updated: 2024-04-30
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
137 participants
INTERVENTIONAL
2013-11-13
2024-03-31
Brief Summary
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Detailed Description
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I. To determine the tolerability of brentuximab vedotin given in combination with standard chemotherapy (anaplastic large cell lymphoma \[ALCL\]99) and to determine the tolerability of crizotinib given in combination with chemotherapy (ALCL99).
II. To estimate the event free survival (EFS) of Arm brentuximab vedotin (BV) and Arm crizotinib (CZ) and contrast these to historical control data.
SECONDARY OBJECTIVES:
I. To determine the prognostic significance of minimal disseminated disease (MDD) at diagnosis and minimal residual disease (MRD) as measured by real-time (RT)-polymerase chain reaction (PCR) in peripheral blood.
OUTLINE: Patients with body surface area (BSA) \< 0.9 m\^2 were non-randomly assigned to Arm BV while it was open and were not eligible for the trial while Arm BV was closed. Patients with BSA \>= 0.9 m\^2 were randomly assigned 1:1 to Arm BV or Arm CZ while both were open and were non-randomly assigned to the open arm while only one of the two arms was open.
ARM BV:
COURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin (1.8 mg/dg/dose - Max dose 180 mg) intravenously (IV) over 30 minutes on day 1, dexamethasone orally (PO) twice daily (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 (1.8 mg/dg/dose - Max dose 180 mg), 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.
ARM CZ:
COURSE A (CYCLES 1, 3, AND 5): Patients receive crizotinib (165 mg/m\^2) 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 (165 mg/m\^2) PO BID as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B.
In all arms, treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm BV (brentuximab vedotin, 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.
Brentuximab Vedotin
Given IV
Cyclophosphamide
Given IV
Cytarabine
Given IT and IV
Dexamethasone
Given PO or IV
Doxorubicin Hydrochloride
Given IV
Etoposide
Given IV
Ifosfamide
Given IV
Methotrexate
Given IT and IV
Arm CZ (crizotinib, combination chemotherapy)
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.
Crizotinib
Given PO
Cyclophosphamide
Given IV
Cytarabine
Given IT and IV
Dexamethasone
Given PO or IV
Doxorubicin Hydrochloride
Given IV
Etoposide
Given IV
Ifosfamide
Given IV
Methotrexate
Given IT and IV
Interventions
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Brentuximab Vedotin
Given IV
Crizotinib
Given PO
Cyclophosphamide
Given IV
Cytarabine
Given IT and IV
Dexamethasone
Given PO or IV
Doxorubicin Hydrochloride
Given IV
Etoposide
Given IV
Ifosfamide
Given IV
Methotrexate
Given IT and IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 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
21 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Eric J Lowe
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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Children's Hospital of Alabama
Birmingham, Alabama, United States
Phoenix Childrens Hospital
Phoenix, 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
Valley Children's Hospital
Madera, California, United States
UCSF Benioff Children's Hospital 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
Naval Medical Center -San Diego
San Diego, California, United States
UCSF Medical Center-Parnassus
San Francisco, California, United States
UCSF Medical Center-Mission Bay
San Francisco, 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 D.C., District of Columbia, 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
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Nicklaus Children's Hospital
Miami, Florida, United States
AdventHealth Orlando
Orlando, Florida, United States
Arnold Palmer Hospital for Children
Orlando, Florida, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
Nemours Children's Hospital
Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States
Johns Hopkins All Children's Hospital
St. 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
Augusta University Medical Center
Augusta, Georgia, United States
Memorial Health University Medical Center
Savannah, Georgia, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, 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
Advocate Children's Hospital-Oak Lawn
Oak Lawn, 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
Blank Children's Hospital
Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Norton Children's Hospital
Louisville, Kentucky, United States
Children's Hospital New Orleans
New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States
Maine Children's Cancer Program
Scarborough, Maine, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 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
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
Columbia Regional
Columbia, Missouri, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Mercy Hospital Saint Louis
St 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
University Medical Center of Southern Nevada
Las Vegas, Nevada, 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
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
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Albany Medical Center
Albany, 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
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering 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
State University of New York Upstate Medical University
Syracuse, New York, United States
Montefiore Medical Center - Moses Campus
The Bronx, 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
Duke University Medical Center
Durham, 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 - Muhlenberg
Bethlehem, Pennsylvania, United States
Penn State Children's Hospital
Hershey, 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
Prisma Health Richland Hospital
Columbia, 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
Saint Jude Children's Research Hospital
Memphis, 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
Children's Hospital of San Antonio
San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Scott and White Memorial Hospital
Temple, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
Inova Fairfax Hospital
Falls Church, Virginia, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
Naval Medical Center - Portsmouth
Portsmouth, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
Seattle Children's Hospital
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States
Madigan Army Medical Center
Tacoma, Washington, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Countries
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References
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Lowe EJ, Reilly AF, Lim MS, Gross TG, Saguilig L, Barkauskas DA, Wu R, Alexander S, Bollard CM. Crizotinib in Combination With Chemotherapy for Pediatric Patients With ALK+ Anaplastic Large-Cell Lymphoma: The Results of Children's Oncology Group Trial ANHL12P1. J Clin Oncol. 2023 Apr 10;41(11):2043-2053. doi: 10.1200/JCO.22.00272. Epub 2022 Dec 19.
Lowe EJ, Reilly AF, Lim MS, Gross TG, Saguilig L, Barkauskas DA, Wu R, Alexander S, Bollard CM. Brentuximab vedotin in combination with chemotherapy for pediatric patients with ALK+ ALCL: results of COG trial ANHL12P1. Blood. 2021 Jul 1;137(26):3595-3603. doi: 10.1182/blood.2020009806.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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NCI-2013-02167
Identifier Type: REGISTRY
Identifier Source: secondary_id
s14-01970
Identifier Type: -
Identifier Source: secondary_id
COG-ANHL12P1
Identifier Type: -
Identifier Source: secondary_id
ANHL12P1
Identifier Type: OTHER
Identifier Source: secondary_id
ANHL12P1
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2013-02167
Identifier Type: -
Identifier Source: org_study_id
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