Childhood Nodular Lymphocyte Predominant Hodgkin LymphomaPhase 3NCT01026220
Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma
A Phase 3 study testing bleomycin sulfate, doxorubicin hydrochloride and liposomal vincristine sulfate in people with Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma and Stage III Childhood Hodgkin Lymphoma, run by Children's Oncology Group at 177 sites in 5 countries.
Trial summary
This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from… Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma, Stage III Childhood Hodgkin Lymphoma, Stage IV Childhood Hodgkin Lymphoma
- What is being tested?
- bleomycin sulfate, doxorubicin hydrochloride and liposomal vincristine sulfate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 166 participants
- Where
- 177 sitesin 5 countries
- Study dates
- 7 Dec 2009to 31 Mar 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Pathologically confirmed newly diagnosed Hodgkin lymphoma (HL) meeting one of the following criteria:
- Classical disease
- Nodular lymphocyte-predominant disease
- Stage III or IV disease with B symptoms, as defined by ≥ 1 of the following:
- Unexplained weight loss > 10% within the past 6 months
- Unexplained recurrent fever > 38°C within the past month
Show all 33Show fewer
- Recurrent drenching night sweats within the past month
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:
- 0.4 mg/dL (1 to 5 months)
- 0.5 mg/dL (6 to 11 months)
- 0.6 mg/dL (12 to 23 months)
- 0.8 mg/dL (2 to 5 years)
- 1 mg/dL (6 to 9 years)
- 1.2 mg/dL (10 to 12 years)
- 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years)
- 1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years)
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- AST or ALT < 2.5 times ULN for age
- Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 50% by MUGA (unless due to large mediastinal mass from HL)
- FEV_1/FVC > 60% by pulmonary function tests (PFT) (unless due to large mediastinal mass fromHL)
- For children who are unable to cooperate for PFTs, the criteria are:
- No evidence of dyspnea at rest
- No exercise intolerance
- Pulse oximetry > 92% on room air
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No pathologic prolongation of QTc interval (> 450 milliseconds) on 12-lead ECG
- No prior chemotherapy, biological response modifiers (e.g., monoclonal antibody therapy), or radiotherapy
- At least 28 days since prior corticosteroids except for emergent treatment for respiratory distress or spinal cord compression, or for treatment of allergy to contrast agent required for CT scan
- No other concurrent cancer chemotherapy or immunomodulating agents (including steroids)
- Concurrent corticosteroid therapy as treatment or prophylaxis for anaphylactic reactions allowed
- No concurrent pegfilgrastim
Who cannot join
None listed.
Trial locations and contacts
177 sites in 5 countries.
177 sites in 5 countries
United States156 sites
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
University of New Mexico
Albuquerque, New Mexico, 87106
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Mission Hospital-Memorial Campus
Asheville, North Carolina, 28801
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Georgia Regents University
Augusta, Georgia, 30912
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
Children's Hospital of Alabama
Birmingham, Alabama, 35233
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Saint Luke's Mountain States Tumor Institute
Boise, Idaho, 83712
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Vermont
Burlington, Vermont, 05401
University of North Carolina
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
West Virginia University Charleston
Charleston, West Virginia, 25304
Carolinas Medical Center
Charlotte, North Carolina, 28203
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
T C Thompson Children's Hospital
Chattanooga, Tennessee, 37403
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
University of Chicago
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Columbia Regional
Columbia, Missouri, 65201
University of Missouri - Ellis Fischel
Columbia, Missouri, 65212
Palmetto Health Richland
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Medical City Dallas Hospital
Dallas, Texas, 75230
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Geisinger Medical Center
Danville, Pennsylvania, 17822-2001
Dayton Children's Hospital
Dayton, Ohio, 45404
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Blank Children's Hospital
Des Moines, Iowa, 50309
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Saint John Hospital and Medical Center
Detroit, Michigan, 48236
Southern California Permanente Medical Group
Downey, California, 90242
City of Hope Medical Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Michigan State University Clinical Center
East Lansing, Michigan, 48824-7016
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Sanford Medical Center-Fargo
Fargo, North Dakota, 58122
Lee Memorial Health System
Fort Myers, Florida, 33901
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234
Cook Children's Medical Center
Fort Worth, Texas, 76104
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, 49503
Saint Vincent Hospital
Green Bay, Wisconsin, 54301
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Greenville Cancer Treatment Center
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, 17033
Memorial Healthcare System - Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
University of Hawaii
Honolulu, Hawaii, 96813
Baylor College of Medicine
Houston, Texas, 77030
Indiana University Medical Center
Indianapolis, Indiana, 46202
Riley Hospital for Children
Indianapolis, Indiana, 46202
Saint Vincent Hospital and Health Services
Indianapolis, Indiana, 46260
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, 32207
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Kalamazoo Center for Medical Studies
Kalamazoo, Michigan, 49008
The Childrens Mercy Hospital
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, 89106
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Kentucky
Lexington, Kentucky, 40536
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Loma Linda University Medical Center
Loma Linda, California, 92354
Miller Children's Hospital
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Kosair Children's Hospital
Louisville, Kentucky, 40202
Covenant Children's Hospital
Lubbock, Texas, 79410
Children's Hospital Central California
Madera, California, 93636-8762
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Marshfield Clinic
Marshfield, Wisconsin, 54449
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Miami Children's Hospital
Miami, Florida, 33155
Baptist Hospital of Miami
Miami, Florida, 33176
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226
Winthrop University Hospital
Mineola, New York, 11501
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455
University of South Alabama
Mobile, Alabama, 36604
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Yale University
New Haven, Connecticut, 06520
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
Children's Hospital-Main Campus
New Orleans, Louisiana, 70118
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Weill Medical College of Cornell University
New York, New York, 10065
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Childrens Hospital-King's Daughters
Norfolk, Virginia, 23507
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453
Children's Hospital and Research Center at Oakland
Oakland, California, 94609-1809
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Childrens Hospital of Orange County
Orange, California, 92868-3874
Florida Hospital
Orlando, Florida, 32803
Nemours Children's Clinic - Orlando
Orlando, Florida, 32806
UF Cancer Center at Orlando Health
Orlando, Florida, 32806
Advocate Lutheran General Hospital.
Park Ridge, Illinois, 60068
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Saint Jude Midwest Affiliate
Peoria, Illinois, 61602
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Oncology Group
Philadelphia, Pennsylvania, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Legacy Emanuel Hospital and Health Center
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239
Rhode Island Hospital
Providence, Rhode Island, 02903
Virginia Commonwealth University
Richmond, Virginia, 23298
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
University of California at Davis Cancer Center
Sacramento, California, 95817
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
University of California San Francisco Medical Center-Parnassus
San Francisco, California, 94143
Santa Barbara Cottage Hospital
Santa Barbara, California, 93102
Seattle Children's Hospital
Seattle, Washington, 98105
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Baystate Medical Center
Springfield, Massachusetts, 01199
Washington University School of Medicine
St Louis, Missouri, 63110
All Children's Hospital
St. Petersburg, Florida, 33701
Overlook Hospital
Summit, New Jersey, 07902
State University of New York Upstate Medical University
Syracuse, New York, 13210
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Madigan Army Medical Center
Tacoma, Washington, 98431
Saint Joseph Children's Hospital of Tampa
Tampa, Florida, 33607
Scott and White Memorial Hospital
Temple, Texas, 76508
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467-2490
The Toledo Hospital/Toledo Children's Hospital
Toledo, Ohio, 43606
New York Medical College
Valhalla, New York, 10595
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Lombardi Comprehensive Cancer Center at Georgetown University
Washington D.C., District of Columbia, 20057
Saint Mary's Hospital
West Palm Beach, Florida, 33407
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Canada13 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
IWK Health Centre
Halifax, Nova Scotia, B3J 3G9
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, K7L 5P9
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, G1V 4G2
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Australia5 sites
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
Women's and Children's Hospital-Adelaide
North Adelaide, South Australia, 5006
Royal Children's Hospital
Parkville, Victoria, 3052
Princess Margaret Hospital for Children
Perth, Western Australia, 6008
Sydney Children's Hospital
Randwick, New South Wales, 2031
Israel2 sites
Schneider Children's Medical Center of Israel
Petah Tikua, 49202
Chaim Sheba Medical Center
Tel HaShomer, 52621
About this study
Official title: A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma
This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To maintain the overall survival (as defined by 4-year "second-event" free survival) for subjects with high risk Hodgkin lymphoma at or above 95%.
SECONDARY OBJECTIVES:
- To maintain 3-year event-free survival for subjects with high risk Hodgkin lymphoma at or above 93%.
II. To maintain comparable overall survival (as defined by 4-year "second-event" free survival) between subjects with high risk Hodgkin lymphoma who have a rapid or slow response to the initial 2 cycles of ABVE-PC* by intensifying therapy through the addition of 2 cycles of ifosfamide/vinorelbine in those with a slow early response.
III. To investigate whether very early response assessment measured by FDG-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.
IV. To describe the patterns of relapse after ABVE-PC* and risk-adapted radiotherapy.
OUTLINE: This is a multicenter study.
INDUCTION THERAPY (ABVE-PC): Patients receive doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2, bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8, etoposide phosphate IV over 1-2 hours on days 1-3, oral prednisone twice daily on days 1-7, and filgrastim* SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
NOTE: *Patients do not receive filgrastim on day 8.
Patients undergo clinical restaging and response assessment after 2 courses of induction therapy. Patients with rapid early response (RER) or slow early response (SER) proceed to consolidation therapy. Patients with progressive disease go off study.
CONSOLIDATION THERAPY: Patients are assigned to 1 of 2 consolidation therapy regimens based on response to induction therapy. Patients who develop progressive disease after induction are taken off protocol therapy.
REGIMEN I (RER): Patients receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
REGIMEN II (SER): Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-30 minutes on days 1 and 5, and filgrastim SC or IV daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
Patients with a continued response after completion of consolidation therapy proceed to risk-adapted radiotherapy.
RISK-ADAPTED RADIOTHERAPY: Beginning at 3 weeks after completion of consolidation chemotherapy, patients undergo radiotherapy once daily, 5 days a week, for 3 weeks (14 fractions) in the absence of unacceptable toxicity or disease progression. Patients classified as RER receive radiation therapy only to sites of bulky disease. Patients classified as SER receive radiation therapy to sites of bulky disease and areas that remain FDG-PET avid after induction therapy.
After completion of study therapy, patients are followed up periodically for 10 years.
- Conditions
- Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma, Stage III Childhood Hodgkin Lymphoma, Stage IV Childhood Hodgkin Lymphoma
- Being tested
- bleomycin sulfate, doxorubicin hydrochloride, liposomal vincristine sulfate, vinorelbine tartrate, cyclophosphamide
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bleomycin sulfateBiological
Also called Blenoxane, BLEO, BLM
Given IV or SC
Also called ADM, ADR, Adria, Adriamycin PFS
Given IV
liposomal vincristine sulfateDrug
Also called liposomal vincristine, Marqibo, vincristine liposomal, vincristine sulfate liposome injection
Given IV
vinorelbine tartrateDrug
Also called Eunades, navelbine ditartrate, NVB, VNB
Given IV
cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV
etoposide phosphateDrug
Also called ETOP, Etopophos
Given IV
prednisoneDrug
Also called DeCortin, Deltra
Given IV
filgrastimBiological
Also called G-CSF, Neupogen
Given IV or SC
ifosfamideDrug
Also called Cyfos, Holoxan, IFF, IFX
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Regimen I (consolidation therapy) | Experimental | Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Receives: Biological: bleomycin sulfate; Drug: doxorubicin hydrochloride; Drug: liposomal vincristine sulfate; Drug: cyclophosphamide; Drug: etoposide phosphate; Drug: prednisone; Biological: filgrastim |
| Regimen II (consolidation therapy) | Experimental | Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Receives: Biological: bleomycin sulfate; Drug: doxorubicin hydrochloride; Drug: liposomal vincristine sulfate; Drug: vinorelbine tartrate; Drug: cyclophosphamide; Drug: etoposide phosphate; Drug: prednisone; Biological: filgrastim; Drug: ifosfamide |
| Induction: all patient | Experimental | All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease. Receives: Drug: doxorubicin hydrochloride; Drug: liposomal vincristine sulfate; Drug: cyclophosphamide; Drug: etoposide phosphate; Drug: prednisone; Biological: filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Second-event-free Survival
Second event here is defined as any relapse/progression of Hodgkin Lymphoma (HL) or a previously reported second malignant neoplasm (SMN), a new SMN, or death after a first event which can be relapse/progression of HL, SMN, biopsy-proven HL following completion of Consolidation for Slow Early Response (SER) patient, positive bilateral bone marrow biopsy following completion of Consolidation for Stage IV patient, or death. If death occurs as the 1st event, it also counts as the 2nd event.
Measured: At 4 years from enrollment
Safety Analysis and Monitoring of Toxic Death
The primary endpoint for safety analysis and monitoring is toxic death, which is death primarily attributable to treatment.
Measured: Within 30 days of protocol treatment at median follow-up of 48 months (range: 1 to 70 months).
Secondary outcomes (6)
Event Free Survival
Survival from enrollment to first event: relapse/progression, second malignancy, or death.
Measured: At 3 years from enrollment
Second-event-free Survival
Second event here is defined as any relapse/progression of Hodgkin Lymphoma (HL) or a previously reported second malignant neoplasm (SMN), a new SMN, or death after a first event which can be relapse/progression of HL, SMN, biopsy-proven HL following completion of Consolidation for Slow Early Response (SER) patient, positive bilateral bone marrow biopsy following completion of Consolidation for Stage IV patient, or death. If death occurs as the 1st event, it also counts as the 2nd event.
Measured: At 4 years from enrollment
Event-free Survival for Rapid Early Response (RER) Positron Emission Tomography(PET)-1 Positive, RER PET-1 Negative
To investigate whether very early response assessment measured by Fluorodeoxyglucose-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.
Measured: 3 years from enrollment
Relapse-free Survival
A description, survival to relapse, of patterns of relapse after Doxorubicin, Bleomycin, Vincristine, Etoposide - Prednisone, Cyclophosphamide (ABVE-PC) and risk-adapted radiotherapy.
Measured: 3 years from enrollment
Grade 3 and 4 Non-hematologic Toxicities During Protocol Therapy
The number of patients that experience Common Terminology Criteria (CTC) Version 4 grade 3 or higher non-hematologic toxicity at any time during protocol therapy.
Measured: During and after completion of study treatment.
Overall Survival
Survival from enrollment to death.
Measured: At 3 years from enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2009 (estimated)
- Study start7 Dec 2009
- Primary completion1 Mar 2012
- Study completion31 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Childhood Nodular Lymphocyte Predominant Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Kara Kelly, MD, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01026220
- Sponsor's protocol ID
- AHOD0831
- Other IDs
- NCI-2011-01994, CDR0000660550, AHOD0831, AHOD0831, U10CA098543
- Status last verified
- Dec 2021
- First submitted
- 3 Dec 2009
- Last updated
- 28 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tie X, Shin M, Lee C, Perlman SB, Huemann Z, Weisman AJ, Castellino SM, Kelly KM, McCarten KM, Alazraki AL, Hu J, Cho SY, Bradshaw TJ. Automatic Quantification of Serial PET/CT Images for Pediatric Hodgkin Lymphoma Using a Longitudinally Aware Segmentation Network. Radiol Artif Intell. 2025 May;7(3):e240229. doi: 10.1148/ryai.240229.
PubMed 39969278Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28.
PubMed 37505794
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT01026220
- Acronym / sponsor ID
- AHOD0831
- Conditions
- Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma, Stage III Childhood Hodgkin Lymphoma, Stage IV Childhood Hodgkin Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 166 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 7 Dec 2009 (actual)
- Primary completion
- 1 Mar 2012 (actual)
- Study completion
- 31 Mar 2022 (actual)
- First posted
- 4 Dec 2009 (estimated)
- Results
- Posted 30 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES:
- To maintain the overall survival (as defined by 4-year "second-event" free survival) for subjects with high risk Hodgkin lymphoma at or above 95%.
SECONDARY OBJECTIVES:
- To maintain 3-year event-free survival for subjects with high risk Hodgkin lymphoma at or above 93%.
II. To maintain comparable overall survival (as defined by 4-year "second-event" free survival) between subjects with high risk Hodgkin lymphoma who have a rapid or slow response to the initial 2 cycles of ABVE-PC* by intensifying therapy through the addition of 2 cycles of ifosfamide/vinorelbine in those with a slow early response.
III. To investigate whether very early response assessment measured by FDG-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.
IV. To describe the patterns of relapse after ABVE-PC* and risk-adapted radiotherapy.
OUTLINE: This is a multicenter study.
INDUCTION THERAPY (ABVE-PC): Patients receive doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2, bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8, etoposide phosphate IV over 1-2 hours on days 1-3, oral prednisone twice daily on days 1-7, and filgrastim* SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
NOTE: *Patients do not receive filgrastim on day 8.
Patients undergo clinical restaging and response assessment after 2 courses of induction therapy. Patients with rapid early response (RER) or slow early response (SER) proceed to consolidation therapy. Patients with progressive disease go off study.
CONSOLIDATION THERAPY: Patients are assigned to 1 of 2 consolidation therapy regimens based on response to induction therapy. Patients who develop progressive disease after induction are taken off protocol therapy.
REGIMEN I (RER): Patients receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
REGIMEN II (SER): Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-30 minutes on days 1 and 5, and filgrastim SC or IV daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
Patients with a continued response after completion of consolidation therapy proceed to risk-adapted radiotherapy.
RISK-ADAPTED RADIOTHERAPY: Beginning at 3 weeks after completion of consolidation chemotherapy, patients undergo radiotherapy once daily, 5 days a week, for 3 weeks (14 fractions) in the absence of unacceptable toxicity or disease progression. Patients classified as RER receive radiation therapy only to sites of bulky disease. Patients classified as SER receive radiation therapy to sites of bulky disease and areas that remain FDG-PET avid after induction therapy.
After completion of study therapy, patients are followed up periodically for 10 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Regimen I (consolidation therapy) | Experimental | Biological: bleomycin sulfate, Drug: doxorubicin hydrochloride, Drug: liposomal vincristine sulfate, Drug: cyclophosphamide, Drug: etoposide phosphate, Drug: prednisone, Biological: filgrastimPatients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. |
| Regimen II (consolidation therapy) | Experimental | Biological: bleomycin sulfate, Drug: doxorubicin hydrochloride, Drug: liposomal vincristine sulfate, Drug: vinorelbine tartrate, Drug: cyclophosphamide, Drug: etoposide phosphate, Drug: prednisone, Biological: filgrastim, Drug: ifosfamidePatients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. |
| Induction: all patient | Experimental | Drug: doxorubicin hydrochloride, Drug: liposomal vincristine sulfate, Drug: cyclophosphamide, Drug: etoposide phosphate, Drug: prednisone, Biological: filgrastimAll patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (33 listed)
- Pathologically confirmed newly diagnosed Hodgkin lymphoma (HL) meeting one of the following criteria:
- Stage III or IV disease with B symptoms, as defined by ≥ 1 of the following:
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- AST or ALT < 2.5 times ULN for age
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bleomycin sulfateAlso: Blenoxane, BLEO, BLMGiven IV or SC | Biological | Regimen I (consolidation therapy), Regimen II (consolidation therapy) |
| doxorubicin hydrochlorideAlso: ADM, ADR, Adria, Adriamycin PFSGiven IV | Drug | Induction: all patient, Regimen I (consolidation therapy), Regimen II (consolidation therapy) |
| liposomal vincristine sulfateAlso: liposomal vincristine, Marqibo, vincristine liposomal, vincristine sulfate liposome injectionGiven IV | Drug | Induction: all patient, Regimen I (consolidation therapy), Regimen II (consolidation therapy) |
| vinorelbine tartrateAlso: Eunades, navelbine ditartrate, NVB, VNBGiven IV | Drug | Regimen II (consolidation therapy) |
| cyclophosphamideAlso: CPM, CTX, Cytoxan, EndoxanGiven IV | Drug | Induction: all patient, Regimen I (consolidation therapy), Regimen II (consolidation therapy) |
| etoposide phosphateAlso: ETOP, EtopophosGiven IV | Drug | Induction: all patient, Regimen I (consolidation therapy), Regimen II (consolidation therapy) |
| prednisoneAlso: DeCortin, DeltraGiven IV | Drug | Induction: all patient, Regimen I (consolidation therapy), Regimen II (consolidation therapy) |
| filgrastimAlso: G-CSF, NeupogenGiven IV or SC | Biological | Induction: all patient, Regimen I (consolidation therapy), Regimen II (consolidation therapy) |
| ifosfamideAlso: Cyfos, Holoxan, IFF, IFXGiven IV | Drug | Regimen II (consolidation therapy) |
Primary outcome
Second-event-free Survival
Time frame: At 4 years from enrollment
Second event here is defined as any relapse/progression of Hodgkin Lymphoma (HL) or a previously reported second malignant neoplasm (SMN), a new SMN, or death after a first event which can be relapse/progression of HL, SMN, biopsy-proven HL following completion of Consolidation for Slow Early Response (SER) patient, positive bilateral bone marrow biopsy following completion of Consolidation for Stage IV patient, or death. If death occurs as the 1st event, it also counts as the 2nd event.
Safety Analysis and Monitoring of Toxic Death
Time frame: Within 30 days of protocol treatment at median follow-up of 48 months (range: 1 to 70 months).
The primary endpoint for safety analysis and monitoring is toxic death, which is death primarily attributable to treatment.
6 secondary outcomes
Event Free Survival
Time frame: At 3 years from enrollment
Second-event-free Survival
Time frame: At 4 years from enrollment
Event-free Survival for Rapid Early Response (RER) Positron Emission Tomography(PET)-1 Positive, RER PET-1 Negative
Time frame: 3 years from enrollment
Relapse-free Survival
Time frame: 3 years from enrollment
Grade 3 and 4 Non-hematologic Toxicities During Protocol Therapy
Time frame: During and after completion of study treatment.
Overall Survival
Time frame: At 3 years from enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39969278Tie X, Shin M, Lee C, Perlman SB, Huemann Z, Weisman AJ, Castellino SM, Kelly KM, McCarten KM, Alazraki AL, Hu J, Cho SY, Bradshaw TJ. Automatic Quantification of Serial PET/CT Images for Pediatric Hodgkin Lymphoma Using a Longitudinally Aware Segmentation Network. Radiol Artif Intell. 2025 May;7(3):e240229. doi: 10.1148/ryai.240229.
- Derived from this study: PubMed 37505794Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28.
- Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data ArchiveLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kara Kelly, MD principal investigator
Children's Oncology Group
177 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing bleomycin sulfate, doxorubicin hydrochloride and liposomal vincristine sulfate in people with Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma and Stage III Childhood Hodgkin Lymphoma, run by Children's Oncology Group at 177 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 177 sites in United States, Canada, Australia, Israel, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Second-event-free Survival (time frame: At 4 years from enrollment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01026220, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2022.