Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients With Relapsed or Refractory Hodgkin Lymphoma
NCT ID: NCT01780662
Last Updated: 2021-10-28
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
46 participants
INTERVENTIONAL
2013-01-31
2021-09-30
Brief Summary
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Detailed Description
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I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of brentuximab vedotin in combination with gemcitabine administered every three weeks to children with relapsed or primary refractory Hodgkin lymphoma (HL).
II. To define and describe the toxicities of brentuximab vedotin in combination with gemcitabine administered on this schedule.
III. To determine the complete response (CR) rate after treatment with four cycles of gemcitabine with brentuximab vedotin among patients with relapsed or refractory HL.
SECONDARY OBJECTIVES:
I. To preliminarily define the antitumor activity of brentuximab vedotin in combination with gemcitabine within the confines of a Phase 1 study.
II. To describe the overall response rate (ORR) after 4 cycles of therapy among patients with relapsed or refractory HL.
III. To describe the proportion of patients with HL able to mobilize an adequate yield of cluster of differentiation (CD) 34+ stem cells after gemcitabine with brentuximab vedotin.
IV. To describe the relationship between disease response among patients with HL and changes in thymus and activation-regulated chemokine (TARC) during treatment, and to determine if specific micro ribonucleic acid (miRNA) profiles correlate with response to treatment.
V. To describe the frequency of the Fc gamma receptor IIIa (FcγRIIIa)-158 valine (V)/phenylalanine (F) polymorphism among patients who experience pulmonary toxicity on this protocol.
OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study. (Phase I completed as of amendment 4)
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and gemcitabine hydrochloride IV over 100 minutes on days 1 and 8. Treatment repeats every 21 days for up to 15 more courses in the absence of disease progression or unacceptable toxicity. Patients with CR after any course may go off protocol therapy for stem cell transplant.
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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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (brentuximab vedotin, gemcitabine hydrochloride)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and gemcitabine hydrochloride IV over 100 minutes on days 1 and 8. Treatment repeats every 21 days for up to 15 more courses in the absence of disease progression or unacceptable toxicity. Patients with CR after any course may go off protocol therapy for stem cell transplant.
Brentuximab Vedotin
Given IV
Gemcitabine Hydrochloride
Given IV
Interventions
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Brentuximab Vedotin
Given IV
Gemcitabine Hydrochloride
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* PARTS A AND B: Patients with Hodgkin lymphoma (HL) are eligible for both the phase 1 and 2 portions, if they are in one of the following categories:
* Primary refractory disease (i.e. no prior CR)
* Very early relapse (\< 6 months from the end of initial therapy, including chemotherapy ± radiation)
* Advanced stage (III or IV) at diagnosis who relapse less than one year from the end of initial therapy
* Note that patients with low-stage disease (IA or IIA) at initial diagnosis, who were treated with radiation alone or fewer than four cycles of chemotherapy will NOT be eligible
* Patients must have measurable disease, documented by clinical and radiographic criteria
* Patients must have a life expectancy of \>= 8 weeks (\>= 56 days)
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
* At least 14 days after the last dose of myelosuppressive chemotherapy (28 days if prior nitrosourea); Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of therapy
* At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; 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; the duration of this interval must be discussed with the study chair
* At least 7 days after the last dose of 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; the duration of this interval must be discussed with the study chair
* At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
* At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
* At least 14 days after local palliative radiation therapy (XRT) (small port); at least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
* Patients with prior autologous or allogeneic stem cell transplant (SCT) are excluded from this study
* At least 28 days must have elapsed since the most recent dose of bleomycin, to allow adequate time to detect evidence of bleomycin-related pulmonary toxicity
* PART A: FOR PATIENTS WITH KNOWN BONE MARROW INVOLVEMENT (Completed as of Amendment 4)
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* PART B: FOR PATIENTS WITHOUT KNOWN BONE MARROW INVOLVEMENT
* Peripheral absolute neutrophil count (ANC) \>= 750/uL
* Platelet count \>= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* Patients with lymphoma metastatic to bone marrow who have granulocytopenia, anemia, and/or thrombocytopenia will be eligible for study but not evaluable for hematologic toxicity (in Part A, there will be a maximum of one per cohort); such patients must meet the blood counts as in Part A (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled in Part A must be evaluable for hematologic toxicity
* 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:
* =\< 0.6 mg/dL (for 1 to \< 2 years of age)
* =\< 0.8 mg/dL (for 2 to \< 6 years of age)
* =\< 1.0 mg/dL (for 6 to \< 10 years of age)
* =\< 1.2 mg/dL (for 10 to \< 13 years of age)
* =\< 1.4 mg/dL (for females \>= 13 years of age)
* =\< 1.5 mg/dL (for males 13 to \< 16 years of age)
* =\< 1.7 mg/dL (for males \>= 16 years of age)
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for SGPT is 45 U/L
* Serum albumin \>= 2 g/dL
* No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry \> 92% while breathing room air
* Forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) \> 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and forced vital capacity all \> 50% predicted value; Note: pulmonary function testing is not required for children \< 8 years old, or for any child who is developmentally unable to comply with pulmonary function testing
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 4) resulting from prior therapy must be \< grade 2
Exclusion Criteria
* Concomitant medications
* Patients receiving stable or decreasing corticosteroids are not eligible for other concurrent conditions (e.g. asthma, autoimmune diseases, rash, documented adrenal insufficiency) are eligible for this study
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients with an immunodeficiency that existed prior to diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and children on current systemic immunosuppressive agents are not eligible
* Patients known to be positive for human immunodeficiency virus (HIV) are not eligible
* Prior therapy
* Patients with prior exposure to brentuximab vedotin are not eligible; NOTE: prior exposure to gemcitabine is NOT an exclusion criterion
* Patients who have undergone prior autologous or allogeneic SCT are not eligible
* Patients with HL who were stage IA or IIA at initial diagnosis and treated with either radiation alone or \< 4 cycles of chemotherapy are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients with known hypersensitivity to Escherichia coli (E.coli)-derived proteins, filgrastim, or any component of filgrastim are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
* All patients and/or their parents or legal guardians 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
13 Months
30 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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Peter D Cole
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
Kaiser Permanente Downey Medical Center
Downey, California, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Children's Hospital Los Angeles
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
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Yale University
New Haven, Connecticut, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 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
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, 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
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
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
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
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
Blank Children's Hospital
Des Moines, Iowa, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 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
Baystate Medical Center
Springfield, Massachusetts, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Ascension Saint John Hospital
Detroit, Michigan, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, 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
St Louis, Missouri, 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
Dartmouth Hitchcock Medical 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
Albany Medical Center
Albany, New York, United States
Roswell Park Cancer Institute
Buffalo, 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
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
New York Medical College
Valhalla, New York, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 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
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
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
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States
Saint Jude Children's Research Hospital
Memphis, 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
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, 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
Primary Children's Hospital
Salt Lake City, Utah, United States
Children's Hospital of The King's Daughters
Norfolk, 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
Madigan Army Medical Center
Tacoma, Washington, United States
West Virginia University Healthcare
Morgantown, West Virginia, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada
Kingston Health Sciences Centre
Kingston, Ontario, Canada
Children's Hospital
London, 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
Centre Hospitalier Universitaire de Quebec
Québec, , Canada
Countries
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References
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Cole PD, McCarten KM, Pei Q, Spira M, Metzger ML, Drachtman RA, Horton TM, Bush R, Blaney SM, Weigel BJ, Kelly KM. Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma (AHOD1221): a Children's Oncology Group, multicentre single-arm, phase 1-2 trial. Lancet Oncol. 2018 Sep;19(9):1229-1238. doi: 10.1016/S1470-2045(18)30426-1. Epub 2018 Aug 16.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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NCI-2013-00107
Identifier Type: REGISTRY
Identifier Source: secondary_id
AHOD1221
Identifier Type: -
Identifier Source: secondary_id
COG-AHOD1221
Identifier Type: -
Identifier Source: secondary_id
AHOD1221
Identifier Type: OTHER
Identifier Source: secondary_id
AHOD1221
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2013-00107
Identifier Type: -
Identifier Source: org_study_id