Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients With Relapsed or Refractory Hodgkin Lymphoma
A Phase 1/2 Study of Brentuximab Vedotin (SGN35) in Combination With Gemcitabine for Pediatric and Young Adult Patients With Relapsed or Refractory Hodgkin Lymphoma
5 other identifiers
interventional
46
2 countries
116
Brief Summary
This phase I/II trial studies the side effects and the best dose of brentuximab vedotin when given together with gemcitabine hydrochloride and to see how well they work in treating younger patients with Hodgkin lymphoma that has returned or does not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may find cancer cells and help kill them. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin together with gemcitabine hydrochloride may kill more cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jan 2013
Longer than P75 for phase_1
116 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 29, 2013
CompletedFirst Posted
Study publicly available on registry
January 31, 2013
CompletedStudy Start
First participant enrolled
January 31, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2017
CompletedResults Posted
Study results publicly available
October 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2021
CompletedOctober 28, 2021
October 1, 2021
4.7 years
January 29, 2013
February 7, 2019
October 5, 2021
Conditions
Outcome Measures
Primary Outcomes (3)
Maximum Tolerated Dose (MTD) for Brentuximab Vedotin
MTD was determined as the maximum dose at which fewer than one-third of patients experience Dose Limiting Toxicities (DLT) as assessed by National Cancer Institute (NCI) CTCAE v 4.0 during Cycle 1 of therapy. Gemcitabine was administered on days 1 and 8 of a 21 day cycle at a fixed dose. Brentuximab vedotin was investigated at a starting dose of 1.4 mg/kg administered on day 1 and escalated if tolerated.
During cycle 1 of protocol therapy (21 days)
Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
The number of eligible patients assigned to receive brentuximab vedotin in combination with gemcitabine that experienced CTC Version 4, grade 3 or higher adverse events during Phase 1 and Phase 2.
13 months from first dose
The Number of Patients With Relapsed or Refractory HL Who Achieved Complete Response (CR)
The number of patients who experienced complete Response (CR) within the first four cycles. By modern response criteria, those with partial response (PR) or stable disease with all target lesions with Deauville scores \<=3 after cycle 4 are also considered as CR. Patients were assessed after treatment with four cycles of gemcitabine with brentuximab vedotin. CR was only reported for Dose level 2 across both phases of study.
After 4 cycles (21 days per cycle) of protocol therapy
Secondary Outcomes (6)
The Number of Patients Who Had Disease Response Assessed by Deauville Scales Among Those in Phase I With Dose Level 2.
Up to 13 months from first dose
Percentage of Patients Who Achieved Overall Response (OR) as Measured by Complete Response (CR) and Partial Response (PR)
After 4 cycles (21 days per cycle) of protocol therapy
The Number of Patients Who Had Successful Peripheral Blood Stem Cell (PBSC) Collection
From 1 to 5 cycles
Plasma Level of Thymus and Activation-Regulated Chemokine (TARC)
From baseline to time prior to cycle 2
Correlation Between Micro Ribonucleic Acid (miRNA) and Disease Response to Protocol Treatment
From the end of first dose to the end of last dose (Up to 13 Months)
- +1 more secondary outcomes
Study Arms (1)
Treatment (brentuximab vedotin, gemcitabine hydrochloride)
EXPERIMENTALPatients 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.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have had histologic verification of the malignancy at original diagnosis; patients must have histologic verification of recurrent Hodgkin disease at the time of relapse; no additional biopsy is required for patients with primary refractory disease (i.e. no prior CR)
- 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
- +26 more criteria
You may not qualify if:
- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during protocol therapy and for at least 30 days after the last dose of brentuximab vedotin; abstinence is an acceptable method of birth control
- 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 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
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (116)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, 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
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Yale University
New Haven, Connecticut, 06520, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Children's National Medical Center
Washington D.C., 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
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, 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
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
St. Petersburg, Florida, 33701, United States
Saint Mary's Hospital
West Palm Beach, Florida, 33407, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Memorial Health University Medical Center
Savannah, Georgia, 31404, 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
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
Blank Children's Hospital
Des Moines, Iowa, 50309, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, 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
Baystate Medical Center
Springfield, Massachusetts, 01199, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Ascension Saint John Hospital
Detroit, Michigan, 48236, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, 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
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
Albany Medical Center
Albany, New York, 12208, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
University of Rochester
Rochester, New York, 14642, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
New York Medical College
Valhalla, New York, 10595, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, 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
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
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
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, 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
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, 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
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, 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
Madigan Army Medical Center
Tacoma, Washington, 98431, United States
West Virginia University Healthcare
Morgantown, West Virginia, 26506, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5, Canada
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7, Canada
Children's Hospital
London, Ontario, N6A 5W9, Canada
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
Centre Hospitalier Universitaire de Quebec
Québec, G1V 4G2, Canada
Related Publications (1)
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.
PMID: 30122620DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Samples have been banked, but data will never be analyzed for Outcome measure #8, Correlation between micro ribonucleic acid (miRNA) and disease response to protocol treatment.
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Peter D Cole
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 29, 2013
First Posted
January 31, 2013
Study Start
January 31, 2013
Primary Completion
September 30, 2017
Study Completion
September 30, 2021
Last Updated
October 28, 2021
Results First Posted
October 1, 2019
Record last verified: 2021-10