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

Lymphoma Clinical Trial

Official title:

A Phase I/II Study of Gemcitabine (GEMZAR)/Vinorelbine (NAVELBINE)/Liposomal Doxorubicin (DOXIL) in Relapsed/Refractory Hodgkin's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006029
• Other study ID #: CALGB-59804
• Secondary ID: CLB-59804CDR0000
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 5, 2000
• Last updated: July 12, 2016
• Start date: July 2000
• Est. completion date: February 2007

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

Intervention

Drug:
• gemcitabine hydrochloride

• pegylated liposomal doxorubicin hydrochloride

• vinorelbine tartrate

Locations

Country	Name	City	State
Puerto Rico	University of Puerto Rico School of Medicine Medical Sciences Campus	San Juan
United States	Northeast Alabama Regional Medical Center	Anniston	Alabama
United States	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina
United States	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Veterans Affairs Medical Center - Baltimore	Baltimore	Maryland
United States	Green Mountain Oncology Group	Bennington	Vermont
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Veterans Affairs Medical Center - Buffalo	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Cooper University Hospital	Camden	New Jersey
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Martha Jefferson Hospital	Charlottesville	Virginia
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	NorthEast Oncology Associates	Concord	North Carolina
United States	Veterans Affairs Medical Center - Dallas	Dallas	Texas
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Veterans Affairs Medical Center - Durham	Durham	North Carolina
United States	Elmhurst Hospital Center	Elmhurst	New York
United States	Veterans Affairs Medical Center - Fargo	Fargo	North Dakota
United States	Cape Fear Valley Health System	Fayetteville	North Carolina
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Fort Wayne Medical Oncology and Hematology, Incorporated	Fort Wayne	Indiana
United States	Memorial Regional Hospital Comprehensive Cancer Center	Hollywood	Florida
United States	St. Mary's Medical Center	Huntington	West Virginia
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Queens Cancer Center of Queens Hospital	Jamaica	New York
United States	Lenoir Memorial Hospital Cancer Center	Kinston	North Carolina
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Veterans Affairs Medical Center - Las Vegas	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Baptist Hospital East - Louisville	Louisville	Kentucky
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	North Shore University Hospital	Manhasset	New York
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center, NY	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Virginia Oncology Associates - Norfolk	Norfolk	Virginia
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina
United States	Lifespan: The Miriam Hospital	Providence	Rhode Island
United States	Ministry Medical Group - Northern Region	Rhinelander	Wisconsin
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia
United States	Saint Anthony Medical Center	Rockford	Illinois
United States	Lakeland Medical Center - St. Joseph	Saint Joseph	Michigan
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Veterans Affairs Medical Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	Lombardi Cancer Center	Washington	District of Columbia
United States	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Helen and Harry Gray Cancer Institute at Good Samaritan Medical Center	West Palm Beach	Florida
United States	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont
United States	New Hanover Regional Medical Center	Wilmington	North Carolina
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (3)

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

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 lymp — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate		Up to 4 years	Yes
Secondary	Overall survival		Up to 4 years	No