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

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00006029

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

Duration (Months)

1.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: gemcitabine hydrochloride Drug: pegylated liposomal doxorubicin hydrochloride Drug: vinorelbine tartrate	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

91 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2000

Actual Primary Completion Date :

Feb 1, 2007

Actual Study Completion Date :

Feb 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: vinorelbine + gemcitabine + doxorubicin - higher doses Patients who have not undergone prior transplantation receive vinorelbine, gemcitabine, and doxorubicin HCl liposome. Patients are followed every 6 months for 2 years and then annually for 6 years.	Drug: gemcitabine hydrochloride Drug: pegylated liposomal doxorubicin hydrochloride Drug: vinorelbine tartrate
Experimental: vinorelbine + gemcitabine + doxorubicin - lower doses Patients who have undergone prior transplantation receive lower doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome. Patients are followed every 6 months for 2 years and then annually for 6 years.	Drug: gemcitabine hydrochloride Drug: pegylated liposomal doxorubicin hydrochloride Drug: vinorelbine tartrate

Arm

Intervention/Treatment

Active Comparator: vinorelbine + gemcitabine + doxorubicin - higher doses

Patients who have not undergone prior transplantation receive vinorelbine, gemcitabine, and doxorubicin HCl liposome. Patients are followed every 6 months for 2 years and then annually for 6 years.

Drug: gemcitabine hydrochloride

Drug: pegylated liposomal doxorubicin hydrochloride

Drug: vinorelbine tartrate

Experimental: vinorelbine + gemcitabine + doxorubicin - lower doses

Patients who have undergone prior transplantation receive lower doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome. Patients are followed every 6 months for 2 years and then annually for 6 years.

Drug: gemcitabine hydrochloride

Drug: pegylated liposomal doxorubicin hydrochloride

Drug: vinorelbine tartrate

Outcome Measures

Primary Outcome Measures

Overall response rate [Up to 4 years]

Secondary Outcome Measures

Overall survival [Up to 4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northeast Alabama Regional Medical Center	Anniston	Alabama	United States	36207
2	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
3	Veterans Affairs Medical Center - San Diego	San Diego	California	United States	92161
4	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
5	Veterans Affairs Medical Center - San Francisco	San Francisco	California	United States	94121
6	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
7	Lombardi Cancer Center	Washington	District of Columbia	United States	20007
8	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5000
9	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia	United States	20422
10	Broward General Medical Center	Fort Lauderdale	Florida	United States	33316
11	Memorial Regional Hospital Comprehensive Cancer Center	Hollywood	Florida	United States	33021
12	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
13	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
14	Helen and Harry Gray Cancer Institute at Good Samaritan Medical Center	West Palm Beach	Florida	United States	33401
15	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois	United States	60612
16	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
17	Louis A. Weiss Memorial Hospital	Chicago	Illinois	United States	60640
18	West Suburban Center for Cancer Care	River Forest	Illinois	United States	60305
19	Saint Anthony Medical Center	Rockford	Illinois	United States	61108
20	Fort Wayne Medical Oncology and Hematology, Incorporated	Fort Wayne	Indiana	United States	46885-5099
21	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa	United States	52722
22	Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242-1009
23	Baptist Hospital East - Louisville	Louisville	Kentucky	United States	40207
24	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
25	Veterans Affairs Medical Center - Baltimore	Baltimore	Maryland	United States	21201
26	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
27	University of Massachusetts Memorial Medical Center - University Campus	Worcester	Massachusetts	United States	01655
28	Lakeland Medical Center - St. Joseph	Saint Joseph	Michigan	United States	49085
29	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55417
30	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
31	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri	United States	65201
32	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri	United States	65203
33	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
34	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
35	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
36	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
37	Veterans Affairs Medical Center - Las Vegas	Las Vegas	Nevada	United States	89106
38	Norris Cotton Cancer Center	Lebanon	New Hampshire	United States	03756-0002
39	Cooper University Hospital	Camden	New Jersey	United States	08103
40	Veterans Affairs Medical Center - Buffalo	Buffalo	New York	United States	14215
41	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
42	Elmhurst Hospital Center	Elmhurst	New York	United States	11373
43	Queens Cancer Center of Queens Hospital	Jamaica	New York	United States	11432
44	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
45	North Shore University Hospital	Manhasset	New York	United States	11030
46	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
47	Weill Medical College of Cornell University	New York	New York	United States	10021
48	Mount Sinai Medical Center, NY	New York	New York	United States	10029
49	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
50	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
51	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York	United States	13217
52	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina	United States	28805
53	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
54	NorthEast Oncology Associates	Concord	North Carolina	United States	28025
55	Veterans Affairs Medical Center - Durham	Durham	North Carolina	United States	27705
56	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
57	Cape Fear Valley Health System	Fayetteville	North Carolina	United States	28302-2000
58	Lenoir Memorial Hospital Cancer Center	Kinston	North Carolina	United States	28503-1678
59	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
60	New Hanover Regional Medical Center	Wilmington	North Carolina	United States	28402-9025
61	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
62	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
63	Veterans Affairs Medical Center - Fargo	Fargo	North Dakota	United States	58102
64	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210-1240
65	Lifespan: The Miriam Hospital	Providence	Rhode Island	United States	02906
66	Veterans Affairs Medical Center - Dallas	Dallas	Texas	United States	75216
67	Green Mountain Oncology Group	Bennington	Vermont	United States	05201
68	Vermont Cancer Center	Burlington	Vermont	United States	05401-3498
69	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont	United States	05009
70	Martha Jefferson Hospital	Charlottesville	Virginia	United States	22901
71	Virginia Oncology Associates - Norfolk	Norfolk	Virginia	United States	23502
72	MBCCOP - Massey Cancer Center	Richmond	Virginia	United States	23298-0037
73	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia	United States	24014
74	St. Mary's Medical Center	Huntington	West Virginia	United States	25701
75	Ministry Medical Group - Northern Region	Rhinelander	Wisconsin	United States	54501
76	University of Puerto Rico School of Medicine Medical Sciences Campus	San Juan		Puerto Rico	00936-5067