Clinical trial NCT00006760: Combination Chemotherapy in Treating Children With Refractory or Relapsed Hodgkin's Lymphoma
Official title: A Pilot Study of Re-Induction Chemotherapy With Ifosfamide, and Vinorelbine (IV) in Children With Refractory/Relapsed Hodgkin's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: recurrent/refractory childhood Hodgkin lymphoma
childhood lymphocyte predominant Hodgkin lymphoma
childhood lymphocyte depletion Hodgkin lymphoma
childhood nodular sclerosis Hodgkin lymphoma
childhood mixed cellularity Hodgkin lymphoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 66
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as ifosfamide and vinorelbine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating children who have refractory or relapsed Hodgkin's lymphoma.

Detailed description: OBJECTIVES:

* Determine the response rate (overall and within strata) in both minimally pretreated, low-risk and heavily pretreated, high-risk children with refractory or relapsed Hodgkin's lymphoma treated with ifosfamide and vinorelbine with filgrastim (G-CSF).
* Determine the cardiac, hepatic, renal, and hematologic toxicity of this regimen in minimally-pretreated, low-risk patients.
* Determine the toxic death rate in minimally pretreated, low-risk patients treated with this regimen.
* Determine whether this treatment regimen can mobilize sufficient hematopoietic stem cells (CD34) for subsequent stem cell transplantation in minimally pretreated, low-risk patients.
* Determine the incidence of hypermutability by longitudinal genotoxic biomonitoring of patients treated with this regimen.
* Determine the prognostic significance of biological markers, including serum interleukin (IL)-10 receptor, serum IL-2 receptor, p53, and mdm-2 in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified by prior therapy (minimally pretreated, low-risk vs heavily pretreated, high-risk).

Patients receive ifosfamide IV over 24 hours on days 1-4 and vinorelbine IV over 6-10 minutes on days 1 and 5. Patients also receive filgrastim (G-CSF) subcutaneously or IV over 15-30 minutes beginning 24-36 hours after completion of vinorelbine and continuing daily until blood counts recover. Treatment repeats at least every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients may receive a third course of therapy at the discretion of the investigator.

Heavily pretreated, high-risk patients who achieve a complete response are eligible for stem cell transplantation. Patients undergo peripheral blood stem cell (PBSC) collection during hematopoietic recovery after the second course of chemotherapy. Patients with sufficient PBSCs collected may undergo PBSC transplantation on protocol COG-AHOD0121.

Patients are followed at 1, 6, and 12 months and then periodically thereafter.

PROJECTED ACCRUAL: A total of 66 patients will be accrued for this study within 1.5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed refractory or relapsed Hodgkin's lymphoma

  * Mixed cellularity, not otherwise specified (NOS)
  * Lymphocytic depletion, NOS
  * Lymphocytic depletion, diffuse fibrosis
  * Lymphocytic depletion, reticular
  * Lymphocytic predominance, NOS
  * Lymphocytic predominance, diffuse
  * Lymphocytic predominance, nodular
  * Hodgkin's paragranuloma NOS
  * Hodgkin's granuloma
  * Hodgkin's sarcoma
  * Nodular sclerosis, NOS
  * Nodular sclerosis, cellular phase
  * Nodular sclerosis, lymphocytic predominance
  * Nodular sclerosis, mixed cellularity
  * Nodular sclerosis, lymphocytic depletion
  * Other (type not specified)
* In first relapse
* Metastasis to bone marrow with granulocytopenia, anemia, and/or thrombocytopenia allowed
* Not enrolled on POG-9426 unless there is an extranodal site of recurrence

PATIENT CHARACTERISTICS:

Age:

* Under 30 at diagnosis

Performance status:

* Lansky 60-100% (for patients 16 years and under)
* Karnofsky 60-100% (for patients over 16 years)

Life expectancy:

* At least 2 months

Hematopoietic:

* See Disease Characteristics
* Absolute neutrophil count at least 1,000/mm\^3
* Platelet count at least 75,000/mm\^3 (transfusion independent)

Hepatic:

* Bilirubin no greater than 1.5 times normal
* SGOT or SGPT less than 2.5 times normal

Renal:

* Creatinine no greater than 1.5 times normal
* Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Cardiovascular:

* Shortening fraction at least 27% by echocardiogram OR
* Ejection fraction at least 50% by gated radionuclide

Other:

* No other concurrent serious illness
* No known hypersensitivity to E. coli-derived proteins, filgrastim (G-CSF), or any other component of study drugs

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent immunomodulating agents

Chemotherapy:

* At least 2 weeks since prior chemotherapy (3 weeks for nitrosoureas) and recovered
* No other concurrent anticancer chemotherapy

Endocrine therapy:

* No concurrent steroids
* No concurrent corticosteroids (e.g., dexamethasone)

Radiotherapy:

* Recovered from prior radiotherapy

Surgery:

* Not specified

Primary outcomes:
measure: Overall response rate
timeFrame: After 2 cycles
Secondary outcomes:
measure: Rate of successful PBSC harvest during re-induction defined as the ability to harvest 5 x 10^6 CD34+ cells/kg
timeFrame: After 2 cycles
measure: Biologic markers
timeFrame: At enrollment and during/after therapy
measure: Cardiac, hepatic, renal, hematologic toxicity
timeFrame: Within 1 month of completion of therapy
measure: Toxic death
timeFrame: Within 1 month of Completion of therapy
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Comprehensive Cancer Center at University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Downey
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Long Beach
country: United States
facility: Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Center - Oakland
state: California
city: San Diego
country: United States
facility: Children's Hospital and Health Center - San Diego
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center at Stanford University Medical Center
state: California
city: Denver
country: United States
facility: Children's Hospital Cancer Center
state: Colorado
city: Farmington
country: United States
facility: Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Lee Cancer Care of Lee Memorial Health System
state: Florida
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute at Florida Hospital Orlando
state: Florida
city: Orlando
country: United States
facility: M.D. Anderson Cancer Center - Orlando
state: Florida
city: Pensacola
country: United States
facility: Sacred Heart Cancer Center at Sacred Heart Hospital
state: Florida
city: St. Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Cancer Institute at St. Joseph's Hospital
state: Florida
city: West Palm Beach
country: United States
facility: Kaplan Cancer Center at St. Mary's Medical Center
state: Florida
city: Savannah
country: United States
facility: Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Boise
country: United States
facility: St. Luke's Mountain States Tumor Institute - Boise
state: Idaho
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Indianapolis Hospital
state: Indiana
city: Des Moines
country: United States
facility: Blank Children's Hospital
state: Iowa
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Children's Hospital of New Orleans
state: Louisiana
city: Bangor
country: United States
facility: CancerCare of Maine at Eastern Maine Medial Center
state: Maine
city: Scarborough
country: United States
facility: Maine Children's Cancer Program
state: Maine
city: Baltimore
country: United States
facility: Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Cancer Care - Butterworth Campus
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospital of Minnesota - Minneapolis
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Keesler AFB
country: United States
facility: Keesler Medical Center - Keesler Air Force Base
state: Mississippi
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center Cancer Center
state: New Jersey
city: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: Brooklyn
country: United States
facility: Brooklyn Hospital Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Stony Brook
country: United States
facility: Long Island Cancer Center at Stony Brook University Hospital
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Dayton
country: United States
facility: Children's Medical Center - Dayton
state: Ohio
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Institute of Oncology at Vilnius University
state: Oregon
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System Cancer Center
state: South Carolina
city: Chattanooga
country: United States
facility: T.C. Thompson Children's Hospital
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University Health Sciences Center School of Medicine
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Lubbock
country: United States
facility: Covenant Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Fairfax
country: United States
facility: INOVA Fairfax Hospital
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Massey Cancer Center at Virginia Commonwealth University
state: Virginia
city: Roanoke
country: United States
facility: Carilion Cancer Center of Western Virginia
state: Virginia
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center - Tacoma
state: Washington
city: Huntington
country: United States
facility: Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
state: West Virginia
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Randwick
country: Australia
facility: Prince of Wales Private Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Institute for Cancer Research at Westmead Hospital
state: New South Wales
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Children's & Women's Hospital of British Columbia
state: British Columbia
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital at McGill University Health Center
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
city: Ste-Foy
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre at Pasqua Hospital
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre at the University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Tanya Trippett, MD
role: STUDY_CHAIR
affiliation: St. Jude Children's Research Hospital
name: Pedro A. de Alarcon, MD
role: STUDY_CHAIR
References: