Clinical trial NCT00006029: Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma
Official title: A Phase I/II Study of Gemcitabine (GEMZAR)/Vinorelbine (NAVELBINE)/Liposomal Doxorubicin (DOXIL) in Relapsed/Refractory Hodgkin's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 91
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

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

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose and toxicity of gemcitabine, vinorelbine, and doxorubicin HCl liposome in patients with relapsed or refractory Hodgkin's lymphoma.
* Determine the complete and partial response rates of patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study.

Phase I:

* Patients receive vinorelbine IV over 6-10 minutes, gemcitabine IV over 30 minutes, and doxorubicin HCl liposome IV over 30-60 minutes on days 1 and 8. Treatment continues every 21 days for 2-6 courses in the absence of unacceptable toxicity or disease progression. Patients who respond to treatment after 2 or more courses may stop protocol therapy to undergo peripheral blood stem cell transplantation.

Cohorts of 3-6 patients receive escalating doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with gemcitabine, vinorelbine, and doxorubicin HCl liposome at the recommended phase II dose.

Phase II:

* Patients are assigned to 1 of 2 treatment groups.

  * Group 1: Patients who have not undergone prior transplantation receive vinorelbine, gemcitabine, and doxorubicin HCl liposome as in phase I.
  * Group 2: Patients who have undergone prior transplantation receive lower doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome as in group 1.

Patients are followed every 6 months for 2 years and then annually for 6 years.

PROJECTED ACCRUAL: Approximately 3-100 patients (3-42 for phase I and 20-58 for phase II \[29 per group\]) will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed Hodgkin's lymphoma that is recurrent or refractory after standard chemotherapy

  * Core biopsy is acceptable if adequate tissue is obtained for primary diagnosis and immunophenotyping
  * Bone marrow biopsy is not acceptable as sole means of diagnosis
* Measurable disease

  * Tumor mass greater than 1 cm

PATIENT CHARACTERISTICS:

Age:

* Any age

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 2.0 mg/dL unless history of Gilbert's disease
* AST no greater than 2 times upper limit of normal

Renal:

* Creatinine no greater than 2.0 mg/dL

Cardiovascular:

* LVEF at least 45% by MUGA (for patients whose lifetime cumulative doxorubicin dose exceeds 400 mg/m\^2)

Other:

* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

* No prior gemcitabine, vinorelbine, or doxorubicin HCl liposome
* No other concurrent chemotherapy

Endocrine therapy:

* No concurrent hormones except for nondisease-related conditions (e.g., insulin for diabetes) or steroids for adrenal failure
* No concurrent dexamethasone or other steroidal antiemetics

Primary outcomes:
measure: Overall response rate
timeFrame: Up to 4 years
Secondary outcomes:
measure: Overall survival
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Northeast Alabama Regional Medical Center
state: Alabama
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: San Diego
country: United States
facility: Veterans Affairs Medical Center - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Veterans Affairs Medical Center - San Francisco
state: California
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Veterans Affairs Medical Center - Washington, DC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital Comprehensive Cancer Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: West Palm Beach
country: United States
facility: Helen and Harry Gray Cancer Institute at Good Samaritan Medical Center
state: Florida
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Rockford
country: United States
facility: Saint Anthony Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Incorporated
state: Indiana
city: Bettendorf
country: United States
facility: Hematology Oncology Associates of the Quad Cities
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
city: Louisville
country: United States
facility: Baptist Hospital East - Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Veterans Affairs Medical Center - Baltimore
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center - University Campus
state: Massachusetts
city: Saint Joseph
country: United States
facility: Lakeland Medical Center - St. Joseph
state: Michigan
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Las Vegas
country: United States
facility: Veterans Affairs Medical Center - Las Vegas
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Elmhurst
country: United States
facility: Elmhurst Hospital Center
state: New York
city: Jamaica
country: United States
facility: Queens Cancer Center of Queens Hospital
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Asheville
country: United States
facility: Veterans Affairs Medical Center - Asheville
state: North Carolina
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Concord
country: United States
facility: NorthEast Oncology Associates
state: North Carolina
city: Durham
country: United States
facility: Veterans Affairs Medical Center - Durham
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Fayetteville
country: United States
facility: Cape Fear Valley Health System
state: North Carolina
city: Kinston
country: United States
facility: Lenoir Memorial Hospital Cancer Center
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Moore Regional Hospital
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Regional Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Fargo
country: United States
facility: Veterans Affairs Medical Center - Fargo
state: North Dakota
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Providence
country: United States
facility: Lifespan: The Miriam Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Veterans Affairs Medical Center - Dallas
state: Texas
city: Bennington
country: United States
facility: Green Mountain Oncology Group
state: Vermont
city: Burlington
country: United States
facility: Vermont Cancer Center
state: Vermont
city: White River Junction
country: United States
facility: Veterans Affairs Medical Center - White River Junction
state: Vermont
city: Charlottesville
country: United States
facility: Martha Jefferson Hospital
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Norfolk
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Huntington
country: United States
facility: St. Mary's Medical Center
state: West Virginia
city: Rhinelander
country: United States
facility: Ministry Medical Group - Northern Region
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico School of Medicine Medical Sciences Campus
Study officials:
affiliation: Washington University Siteman Cancer Center
name: Nancy L. Bartlett, MD
role: STUDY_CHAIR
References:
citation: Lai R, Bartlett NL, Mackey JR, Jung SH, Johnson JL, Cook JR, Jones D, Cass CE, Young JD, Said J, Cheson B, Hsi ED. High expression of nucleoside transporter protein hENT1 in Reed-Sternberg cells is associated with treatment failure in relapsed/refractory Hodgkin lymphoma patients treated with gemcitabine, vinorelbine and liposomal doxorubicin - a CALGB 59804 correlative study. Leuk Lymphoma. 2008 Jun;49(6):1202-5. doi: 10.1080/10428190802094237. No abstract available.
citation: Bartlett NL, Niedzwiecki D, Johnson JL, Friedberg JW, Johnson KB, van Besien K, Zelenetz AD, Cheson BD, Canellos GP; Cancer Leukemia Group B. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804. Ann Oncol. 2007 Jun;18(6):1071-9. doi: 10.1093/annonc/mdm090. Epub 2007 Apr 10.
citation: Bartlett N, Niedzwiecki D, Johnson J, et al.: A phase I/II study of gemcitabine, vinorelbine, and liposomal doxorubicin for relapsed Hodgkin's disease: preliminary results of CALGB 59804. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2275, 566, 2003.