Gemcitabine and Vinorelbine in Treating Young Patients With Recurrent or Refractory Hodgkin's Lymphoma

Lymphoma Clinical Trial

Official title:

A Phase II Study Of Weekly Gemcitabine And Vinorelbine In Children With Recurrent Or Refractory Hodgkin's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00070304
• Other study ID #: AHOD0321
• Secondary ID: CDR0000331915COG
• Status: Completed
• Phase: Phase 2
• First received: October 3, 2003
• Last updated: July 25, 2013
• Start date: July 2004

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 gemcitabine and vinorelbine, use 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: This phase II trial is studying how well giving gemcitabine together with vinorelbine works in treating young patients with recurrent or refractory Hodgkin's lymphoma.

Description:

OBJECTIVES:

• Determine the response rate of pediatric patients with recurrent or refractory Hodgkin's lymphoma treated with gemcitabine and vinorelbine.

• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive vinorelbine IV over 6-10 minutes and gemcitabine IV over 100 minutes on days 1 and 8. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 9 and continuing for at least 7 days and until blood counts recover. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease after 2 courses may proceed directly to stem cell transplantation off study OR receive 2 additional courses. Patients with stable disease after 2 courses receive at least 2 additional courses. Patients with continued stable or responding disease (with no disease progression) after 4 courses may continue to receive study treatment for up to 1 year or discontinue study for alternative therapy at the discretion of the treating physician.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 13-26 patients will be accrued for this study within 1.5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 30 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin's lymphoma* with any of the following histologies:

• Not otherwise specified (NOS)

• Mixed cellularity NOS

• Lymphocytic depletion

• NOS

• Diffuse fibrosis

• Reticular

• Lymphocytic predominance

• NOS

• Diffuse

• Nodular

• Paragranuloma

• Granuloma

• Sarcoma

• Nodular sclerosis

• Cellular phase

• NOS

• Lymphocytic predominance

• Mixed cellularity

• Lymphocytic depletion NOTE: *Disease metastatic to bone marrow with granulocytopenia and/or thrombocytopenia is allowed, but is not evaluable for hematological toxicity

• Measurable disease by clinical or radiographic criteria

• Relapsed or refractory to conventional therapy

• Received at least 2 prior cytotoxic chemotherapy regimens

• No stage IA or IIA nodal disease previously treated with any of the following:

• Radiotherapy only

• No more than 4 courses of prior chemotherapy

PATIENT CHARACTERISTICS:

Age

• 30 and under

Performance status

• Karnofsky 50-100% (over 16 years of age)

• Lansky 50-100% (16 and under) OR

• ECOG 0-2

Life expectancy

• At least 8 weeks

Hematopoietic

• See Disease Characteristics

• Absolute neutrophil count = 750/mm^3

• Platelet count = 75,000/mm^3 (transfusion independent, defined as = 3 days since prior platelet transfusion)

Hepatic

• Bilirubin = 1.5 times upper limit of normal (ULN)

• ALT = 2.5 times ULN

Renal

• Creatinine clearance or radioisotope glomerular filtration rate = 70 mL/min OR

• Creatinine based on age as follows:

• No greater than 0.8 mg/dL (age 5 and under)

• No greater than 1.0 mg/dL (age 6 to 10)

• No greater than 1.2 mg/dL (age 11 to 15)

• No greater than 1.5 mg/dL (over age 15)

Pulmonary

• DLCO = 50%

• FEV_1 = 50%

• Vital capacity = 50%

• No evidence of dyspnea at rest

• No exercise intolerance

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after study participation

• Seizure disorder allowed provided patient is on anticonvulsants and disorder is well controlled

• No evidence of active graft-versus-host disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Recovered from prior immunotherapy

• At least 6 months since prior allogeneic stem cell transplantation (SCT)

• At least 7 days since prior biologic agents

• More than 3 months since prior autologous SCT

• More than 1 week since prior growth factors

• No concurrent immunomodulating agents

Chemotherapy

• See Disease Characteristics

• More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered

• No prior gemcitabine and vinorelbine in combination (i.e., administered within 1 week of each other)

• Prior gemcitabine or vinorelbine administered alone is allowed

• No other concurrent chemotherapy

Endocrine therapy

• No concurrent steroids, including corticosteroids as an antiemetic or for control of graft-versus-host disease

• Concurrent corticosteroids allowed only for the following indications:

• Adrenal crisis in patients with suppressed pituitary/adrenal response

• Noncardiogenic pulmonary edema

• Allergic reactions to amphotericin or transfusions treated with low-dose hydrocortisone (less than 100 mg/m^2)

Radiotherapy

• See Disease Characteristics

• At least 3 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• Concurrent immunosuppressive drugs allowed

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
Given by mouth or IV, 5 micrograms/kg/dose (up to 10 micrograms/kg/dose) daily starting on day 9 for a minimum of 7 days and until the ANC is greater to or equal to 1,500/uL.

Drug:
• gemcitabine hydrochloride
Given IV over 100 minutes dose 1000 mg/m2/dose in 500 ml NS on days 1 and 8
• vinorelbine tartrate
Given IV over 6-10 minutes (central venous catheter). Dose 25 mg/m2/dose on days 1 and 8

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	University of Alberta Hospital	Edmonton	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	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	CHUS-Hopital Fleurimont	Sherbrooke	Alberta
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Puerto Rico	San Jorge Children's Hospital	Santurce
Switzerland	Swiss Pediatric Oncology Group Geneva	Geneva
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center Hospital	Albany	New York
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas
United States	C.S. Mott Children's Hospital at University of Michigan Medical Center	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
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	Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham	Birmingham	Alabama
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Floating Hospital for Children at Tufts - New England Medical Center	Boston	Massachusetts
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	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia
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	T.C. Thompson Children's Hospital	Chattanooga	Tennessee
United States	Children's Memorial Hospital - Chicago	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	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Children's Medical Center - Dayton	Dayton	Ohio
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	Duke Comprehensive Cancer Center	Durham	North Carolina
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 Hospital - 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	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	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	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan
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 Cancer Center	Livingston	New Jersey
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	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	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Miami Children's Hospital	Miami	Florida
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota Medical Center & Children's Hospital - Fairview	Minneapolis	Minnesota
United States	Overlook Hospital	Morristown	New Jersey
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	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 Cancer Institute	Oklahoma City	Oklahoma
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Hospital and Health Center & Children's Hospital	Portland	Oregon
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Kaiser Permanente Medical Center - Oakland	Sacramento	California
United States	Primary Children's Medical Center	Salt Lake City	Utah
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	Children's Hospital and Health Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	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	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota
United States	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Siteman Cancer Center at Barnes-Jewish Hospital	St. Louis	Missouri
United States	All Children's Hospital	St. Petersburg	Florida
United States	Stanford Comprehensive Cancer Center - Stanford	Stanford	California
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Madigan Army Medical Center - Tacoma	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health 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	New York Medical College	Valhalla	New York
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
United States	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts
United States	Tod Children's Hospital	Youngstown	Ohio

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Puerto Rico,  Switzerland, 

References & Publications (3)

Cole PD, McCarten KM, Drachtman RA, Alarcon Pd, Chen L, Trippett TM, Schwartz CL. Early [¹8F]fluorodeoxyglucose positron emission tomography-based response evaluation after treatment with gemcitabine and vinorelbine for refractory Hodgkin disease: a child — View Citation

Cole PD, Schwartz CL, Drachtman RA, de Alarcon PA, Chen L, Trippett TM. Phase II study of weekly gemcitabine and vinorelbine for children with recurrent or refractory Hodgkin's disease: a children's oncology group report. J Clin Oncol. 2009 Mar 20;27(9):1 — View Citation

Cole PD, Trippett TM, Drachtman RA: AHOD0321: a COG phase 2 study of weekly gemcitabine and vinorelbine for children with recurrent or refractory Hodgkin disease. [Abstract] Blood 110 (11): A-2318, 2007.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor Response Rate	Adequate tumor response is defined as achieving CR, VGPR or PR at any evaluation.	Up to 1 year	No
Secondary	Toxicities	Toxic death, hepatic, cardiac or renal toxicity, hematologic toxicity, pulmonary toxicity or other grade 3 or 4 toxicities	Up to 4 weeks following the completion of therapy	Yes