Combination Chemotherapy in Treating Children With Refractory or Relapsed Hodgkin's Lymphoma

Lymphoma Clinical Trial

Official title:

A Pilot Study of Re-Induction Chemotherapy With Ifosfamide, and Vinorelbine (IV) in Children With Refractory/Relapsed Hodgkin's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006760
• Other study ID #: AHOD00P1
• Secondary ID: CCG-A5981CDR0000
• Status: Completed
• Phase: Phase 2
• First received: December 6, 2000
• Last updated: July 25, 2013
• Start date: May 2001
• Est. completion date: March 2012

Study information

• Verified date: July 2013
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: March 2012
• Est. primary completion date: July 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 30 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

Intervention

Biological:
• filgrastim
subcutaneously or IV over 15-30 minutes beginning 24-36 hours after completion of vinorelbine and continuing daily until blood counts recover.

Drug:
• ifosfamide
V over 24 hours on days 1-4
• vinorelbine tartrate
IV over 6-10 minutes on days 1 and 5.

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Prince of Wales Private Hospital	Randwick	New South Wales
Australia	Westmead Institute for Cancer Research at Westmead Hospital	Westmead	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Centre Hospitalier Universitaire de Quebec	Ste-Foy	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Texas Tech University Health Sciences Center School of Medicine	Amarillo	Texas
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine
United States	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama
United States	St. Luke's Mountain States Tumor Institute - Boise	Boise	Idaho
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	T.C. Thompson Children's Hospital	Chattanooga	Tennessee
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Children's Medical Center - Dayton	Dayton	Ohio
United States	Children's Hospital Cancer Center	Denver	Colorado
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	INOVA Fairfax Hospital	Fairfax	Virginia
United States	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
United States	Hurley Medical Center	Flint	Michigan
United States	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Spectrum Health Cancer Care - Butterworth Campus	Grand Rapids	Michigan
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Greenville Hospital System Cancer Center	Greenville	South Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	St. Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Keesler Medical Center - Keesler Air Force Base	Keesler AFB	Mississippi
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	St. Barnabas Medical Center	Livingston	New Jersey
United States	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California
United States	Jonsson Comprehensive Cancer Center at UCLA	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	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Miami Children's Hospital	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospital of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Children's Hospital of New Orleans	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	M.D. Anderson Cancer Center - Orlando	Orlando	Florida
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Institute of Oncology at Vilnius University	Portland	Oregon
United States	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia
United States	Carilion Cancer Center of Western Virginia	Roanoke	Virginia
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Kaiser Permanente Medical Center - Oakland	Sacramento	California
United States	Sutter Cancer Center	Sacramento	California
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Children's Hospital and Health Center - San Diego	San Diego	California
United States	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Maine Children's Cancer Program	Scarborough	Maine
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	All Children's Hospital	St. Petersburg	Florida
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	Long Island Cancer Center at Stony Brook University Hospital	Stony Brook	New York
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Madigan Army Medical Center - Tacoma	Tacoma	Washington
United States	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Toledo 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 Medical Center	Washington	District of Columbia
United States	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	Overall response includes complete response (CR) or partial response (PR).	After 2 cycles	No
Secondary	Rate of successful PBSC harvest during re-induction defined as the ability to harvest 5 x 10^6 CD34+ cells/kg	Will be calculated.	After 2 cycles	No
Secondary	Biologic markers		At enrollment and during/after therapy	No
Secondary	Cardiac, hepatic, renal, hematologic toxicity		Within 1 month of completion of therapy	Yes
Secondary	Toxic death		Within 1 month of Completion of therapy	Yes