Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma

Stage IV Childhood Hodgkin Lymphoma Clinical Trial

Official title:

A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01026220
• Other study ID #: AHOD0831
• Secondary ID: NCI-2011-01994CD
• Status: Completed
• Phase: Phase 3
• Start date: December 7, 2009
• Est. completion date: March 31, 2022

Study information

• Verified date: December 2021
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 dividing. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells.

Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: March 31, 2022
• Est. primary completion date: March 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

• 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

• 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

Related Conditions & MeSH terms

• Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma
• Hodgkin Disease
• Lymphoma
• Stage III Childhood Hodgkin Lymphoma
• Stage IV Childhood Hodgkin Lymphoma

Intervention

Biological:
• bleomycin sulfate
Given IV or SC

Drug:
• doxorubicin hydrochloride
Given IV
• liposomal vincristine sulfate
Given IV
• vinorelbine tartrate
Given IV
• cyclophosphamide
Given IV
• etoposide phosphate
Given IV
• prednisone
Given IV

Biological:
• filgrastim
Given IV or SC

Drug:
• ifosfamide
Given IV

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Sydney Children's Hospital	Randwick	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec
Canada	The Montreal Children's Hospital of the MUHC	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Centre Hospitalier Universitaire de Quebec	Ste-Foy	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Israel	Schneider Children's Medical Center of Israel	Petah Tikua
Israel	Chaim Sheba Medical Center	Tel Hashomer
Puerto Rico	San Jorge Children's Hospital	San Juan
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	University of New Mexico	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Mission Hospital-Memorial Campus	Asheville	North Carolina
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Georgia Regents University	Augusta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont	Burlington	Vermont
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston	Charleston	West Virginia
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	T C Thompson Children's Hospital	Chattanooga	Tennessee
United States	Lurie Children's Hospital-Chicago	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Columbia Regional	Columbia	Missouri
United States	Palmetto Health Richland	Columbia	South Carolina
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	City of Hope Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Michigan State University Clinical Center	East Lansing	Michigan
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Medical Center-Fargo	Fargo	North Dakota
United States	Lee Memorial Health System	Fort Myers	Florida
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	BI-LO Charities Children's Cancer Center	Greenville	South Carolina
United States	Greenville Cancer Treatment Center	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Hershey Children's Hospital	Hershey	Pennsylvania
United States	Memorial Healthcare System - Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	University of Hawaii	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Saint Vincent Hospital and Health Services	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic - Jacksonville	Jacksonville	Florida
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan
United States	The Childrens Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Miller Children's Hospital	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Children's Hospital Central California	Madera	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Baptist Hospital of Miami	Miami	Florida
United States	Miami Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota
United States	University of South Alabama	Mobile	Alabama
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	UMDNJ - Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York
United States	Children's Hospital-Main Campus	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Childrens Hospital-King's Daughters	Norfolk	Virginia
United States	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois
United States	Children's Hospital and Research Center at Oakland	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Childrens Hospital of Orange County	Orange	California
United States	Florida Hospital	Orlando	Florida
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	Advocate Lutheran General Hospital.	Park Ridge	Illinois
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Nemours Children's Clinic - Pensacola	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Oncology Group	Philadelphia	Pennsylvania
United States	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	University of California at Davis Cancer Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
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	Rady Children's Hospital - San Diego	San Diego	California
United States	University of California San Francisco Medical Center-Parnassus	San Francisco	California
United States	Santa Barbara Cottage Hospital	Santa Barbara	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Overlook Hospital	Summit	New Jersey
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	Saint Joseph Children's Hospital of Tampa	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	Lombardi Comprehensive Cancer Center at Georgetown University	Washington	District of Columbia
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Israel,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At 4 years from enrollment
Primary	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.	Within 30 days of protocol treatment at median follow-up of 48 months (range: 1 to 70 months).
Secondary	Event Free Survival	Survival from enrollment to first event: relapse/progression, second malignancy, or death.	At 3 years from enrollment
Secondary	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.	At 4 years from enrollment
Secondary	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.	3 years from enrollment
Secondary	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.	3 years from enrollment
Secondary	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.	During and after completion of study treatment.
Secondary	Overall Survival	Survival from enrollment to death.	At 3 years from enrollment

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive