Non Hodgkin Lymphoma Clinical Trial

Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma

Summary

This partially randomized phase II trial studies how well brentuximab vedotin or crizotinib and combination chemotherapy works in treating patients with newly diagnosed stage II-IV anaplastic large cell lymphoma. Brentuximab vedotin is a monoclonal antibody, called brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in targeted way and delivers vedotin to kill them. Crizotinib and methotrexate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether brentuximab vedotin and combination chemotherapy is more effective than crizotinib and combination chemotherapy in treating anaplastic large cell lymphoma.

View Full Description

Full Description

PRIMARY OBJECTIVES:

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.

View Eligibility Criteria

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

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

137

Study ID:

NCT01979536

Recruitment Status:

Active, not recruiting

Sponsor:

National Cancer Institute (NCI)

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There are 151 Locations for this study

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Children's Hospital of Alabama
Birmingham Alabama, 35233, United States
Phoenix Childrens Hospital
Phoenix Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock Arkansas, 72202, United States
Kaiser Permanente Downey Medical Center
Downey California, 90242, United States
City of Hope Comprehensive Cancer Center
Duarte California, 91010, United States
Loma Linda University Medical Center
Loma Linda California, 92354, United States
Miller Children's and Women's Hospital Long Beach
Long Beach California, 90806, United States
Children's Hospital Los Angeles
Los Angeles California, 90027, United States
Cedars Sinai Medical Center
Los Angeles California, 90048, United States
Valley Children's Hospital
Madera California, 93636, United States
UCSF Benioff Children's Hospital Oakland
Oakland California, 94609, United States
Children's Hospital of Orange County
Orange California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto California, 94304, United States
Sutter Medical Center Sacramento
Sacramento California, 95816, United States
University of California Davis Comprehensive Cancer Center
Sacramento California, 95817, United States
Rady Children's Hospital - San Diego
San Diego California, 92123, United States
Naval Medical Center -San Diego
San Diego California, 92134, United States
UCSF Medical Center-Parnassus
San Francisco California, 94143, United States
UCSF Medical Center-Mission Bay
San Francisco California, 94158, United States
Children's Hospital Colorado
Aurora Colorado, 80045, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver Colorado, 80218, United States
Connecticut Children's Medical Center
Hartford Connecticut, 06106, United States
Yale University
New Haven Connecticut, 06520, United States
Alfred I duPont Hospital for Children
Wilmington Delaware, 19803, United States
Children's National Medical Center
Washington District of Columbia, 20010, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers Florida, 33908, United States
University of Florida Health Science Center - Gainesville
Gainesville Florida, 32610, United States
Nemours Children's Clinic-Jacksonville
Jacksonville Florida, 32207, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami Florida, 33136, United States
Nicklaus Children's Hospital
Miami Florida, 33155, United States
AdventHealth Orlando
Orlando Florida, 32803, United States
Arnold Palmer Hospital for Children
Orlando Florida, 32806, United States
Orlando Health Cancer Institute
Orlando Florida, 32806, United States
Nemours Children's Hospital
Orlando Florida, 32827, United States
Nemours Children's Clinic - Pensacola
Pensacola Florida, 32504, United States
Johns Hopkins All Children's Hospital
Saint Petersburg Florida, 33701, United States
Tampa General Hospital
Tampa Florida, 33606, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa Florida, 33607, United States
Saint Mary's Hospital
West Palm Beach Florida, 33407, United States
Children's Healthcare of Atlanta - Egleston
Atlanta Georgia, 30322, United States
Augusta University Medical Center
Augusta Georgia, 30912, United States
Memorial Health University Medical Center
Savannah Georgia, 31404, United States
University of Hawaii Cancer Center
Honolulu Hawaii, 96813, United States
Kapiolani Medical Center for Women and Children
Honolulu Hawaii, 96826, United States
Saint Luke's Cancer Institute - Boise
Boise Idaho, 83712, United States
Lurie Children's Hospital-Chicago
Chicago Illinois, 60611, United States
University of Illinois
Chicago Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago Illinois, 60637, United States
Advocate Children's Hospital-Oak Lawn
Oak Lawn Illinois, 60453, United States
Saint Jude Midwest Affiliate
Peoria Illinois, 61637, United States
Southern Illinois University School of Medicine
Springfield Illinois, 62702, United States
Riley Hospital for Children
Indianapolis Indiana, 46202, United States
Ascension Saint Vincent Indianapolis Hospital
Indianapolis Indiana, 46260, United States
Blank Children's Hospital
Des Moines Iowa, 50309, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City Iowa, 52242, United States
University of Kentucky/Markey Cancer Center
Lexington Kentucky, 40536, United States
Norton Children's Hospital
Louisville Kentucky, 40202, United States
Children's Hospital New Orleans
New Orleans Louisiana, 70118, United States
Ochsner Medical Center Jefferson
New Orleans Louisiana, 70121, United States
Maine Children's Cancer Program
Scarborough Maine, 04074, United States
Sinai Hospital of Baltimore
Baltimore Maryland, 21215, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore Maryland, 21287, United States
Massachusetts General Hospital Cancer Center
Boston Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit Michigan, 48201, United States
Ascension Saint John Hospital
Detroit Michigan, 48236, United States
Michigan State University Clinical Center
East Lansing Michigan, 48824, United States
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids Michigan, 49503, United States
Beaumont Children's Hospital-Royal Oak
Royal Oak Michigan, 48073, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis Minnesota, 55455, United States
Mayo Clinic in Rochester
Rochester Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson Mississippi, 39216, United States
Columbia Regional
Columbia Missouri, 65201, United States
Children's Mercy Hospitals and Clinics
Kansas City Missouri, 64108, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
Mercy Hospital Saint Louis
Saint Louis Missouri, 63141, United States
Children's Hospital and Medical Center of Omaha
Omaha Nebraska, 68114, United States
University of Nebraska Medical Center
Omaha Nebraska, 68198, United States
University Medical Center of Southern Nevada
Las Vegas Nevada, 89102, United States
Sunrise Hospital and Medical Center
Las Vegas Nevada, 89109, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas Nevada, 89135, United States
Summerlin Hospital Medical Center
Las Vegas Nevada, 89144, United States
Dartmouth Hitchcock Medical Center
Lebanon New Hampshire, 03756, United States
Hackensack University Medical Center
Hackensack New Jersey, 07601, United States
Morristown Medical Center
Morristown New Jersey, 07960, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick New Jersey, 08903, United States
Newark Beth Israel Medical Center
Newark New Jersey, 07112, United States
Saint Joseph's Regional Medical Center
Paterson New Jersey, 07503, United States
University of New Mexico Cancer Center
Albuquerque New Mexico, 87102, United States
Albany Medical Center
Albany New York, 12208, United States
Montefiore Medical Center - Moses Campus
Bronx New York, 10467, United States
Roswell Park Cancer Institute
Buffalo New York, 14263, United States
NYU Winthrop Hospital
Mineola New York, 11501, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park New York, 11040, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States
NYP/Weill Cornell Medical Center
New York New York, 10065, United States
University of Rochester
Rochester New York, 14642, United States
State University of New York Upstate Medical University
Syracuse New York, 13210, United States
New York Medical College
Valhalla New York, 10595, United States
Mission Hospital
Asheville North Carolina, 28801, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill North Carolina, 27599, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte North Carolina, 28203, United States
Duke University Medical Center
Durham North Carolina, 27710, United States
Wake Forest University Health Sciences
Winston-Salem North Carolina, 27157, United States
Children's Hospital Medical Center of Akron
Akron Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati Ohio, 45229, United States
Rainbow Babies and Childrens Hospital
Cleveland Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland Ohio, 44195, United States
Nationwide Children's Hospital
Columbus Ohio, 43205, United States
Dayton Children's Hospital
Dayton Ohio, 45404, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo Ohio, 43606, United States
University of Oklahoma Health Sciences Center
Oklahoma City Oklahoma, 73104, United States
Legacy Emanuel Children's Hospital
Portland Oregon, 97227, United States
Oregon Health and Science University
Portland Oregon, 97239, United States
Lehigh Valley Hospital - Muhlenberg
Bethlehem Pennsylvania, 18017, United States
Penn State Children's Hospital
Hershey Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia Pennsylvania, 19104, United States
Saint Christopher's Hospital for Children
Philadelphia Pennsylvania, 19134, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh Pennsylvania, 15224, United States
Rhode Island Hospital
Providence Rhode Island, 02903, United States
Medical University of South Carolina
Charleston South Carolina, 29425, United States
Prisma Health Richland Hospital
Columbia South Carolina, 29203, United States
BI-LO Charities Children's Cancer Center
Greenville South Carolina, 29605, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls South Dakota, 57117, United States
T C Thompson Children's Hospital
Chattanooga Tennessee, 37403, United States
East Tennessee Childrens Hospital
Knoxville Tennessee, 37916, United States
Saint Jude Children's Research Hospital
Memphis Tennessee, 38105, United States
The Children's Hospital at TriStar Centennial
Nashville Tennessee, 37203, United States
Vanderbilt University/Ingram Cancer Center
Nashville Tennessee, 37232, United States
Dell Children's Medical Center of Central Texas
Austin Texas, 78723, United States
Driscoll Children's Hospital
Corpus Christi Texas, 78411, United States
Medical City Dallas Hospital
Dallas Texas, 75230, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas Texas, 75390, United States
El Paso Children's Hospital
El Paso Texas, 79905, United States
Cook Children's Medical Center
Fort Worth Texas, 76104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston Texas, 77030, United States
Children's Hospital of San Antonio
San Antonio Texas, 78207, United States
Methodist Children's Hospital of South Texas
San Antonio Texas, 78229, United States
University of Texas Health Science Center at San Antonio
San Antonio Texas, 78229, United States
Scott and White Memorial Hospital
Temple Texas, 76508, United States
Primary Children's Hospital
Salt Lake City Utah, 84113, United States
Inova Fairfax Hospital
Falls Church Virginia, 22042, United States
Children's Hospital of The King's Daughters
Norfolk Virginia, 23507, United States
Naval Medical Center - Portsmouth
Portsmouth Virginia, 23708, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond Virginia, 23298, United States
Seattle Children's Hospital
Seattle Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane Washington, 99204, United States
Mary Bridge Children's Hospital and Health Center
Tacoma Washington, 98405, United States
Madigan Army Medical Center
Tacoma Washington, 98431, United States
University of Wisconsin Carbone Cancer Center
Madison Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee Wisconsin, 53226, United States

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

137

Study ID:

NCT01979536

Recruitment Status:

Active, not recruiting

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

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