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A Randomized Phase III Trial Comparing Early High Dose Chemotherapy and an Autologous Stem Cell Transplant to Conventional Dose ABVD Chemotherapy for Patients With Advanced Stage Poor Prognosis Hodgkin's Disease as Defined by the International Prognostic Factors Project on Advanced Hodgkin's Disease


Phase 3
15 Years
65 Years
Not Enrolling
Both
Lymphoma

Thank you

Trial Information

A Randomized Phase III Trial Comparing Early High Dose Chemotherapy and an Autologous Stem Cell Transplant to Conventional Dose ABVD Chemotherapy for Patients With Advanced Stage Poor Prognosis Hodgkin's Disease as Defined by the International Prognostic Factors Project on Advanced Hodgkin's Disease


OBJECTIVES:

- Compare progression-free and overall survival of patients with stage III or IV
Hodgkin's disease treated with doxorubicin, bleomycin, vinblastine, and dacarbazine
with or without autologous peripheral blood stem cell transplantation and high-dose
chemotherapy.

- Compare the toxic effects of these treatment regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
number of poor prognostic factors (3 vs 4 vs 5) and stage of disease (III vs IV).

Patients receive induction chemotherapy consisting of doxorubicin IV over 5 minutes,
bleomycin IV over 10 minutes, vinblastine IV over 5 minutes, and dacarbazine IV over 15-30
minutes on days 1 and 15. Treatment repeats every 28 days for 5 courses in the absence of
disease progression or unacceptable toxicity. Patients who show at least partial response
after the fifth course of induction chemotherapy and whose blood counts have recovered are
randomized to 1 of 2 treatment arms.

- Arm I: Patients receive 3 additional courses of induction chemotherapy for a total of 8
courses.

- Arm II: Patients receive 1 additional course of induction chemotherapy followed by stem
cell collection. Patients then receive high-dose chemotherapy with carmustine IV over 2
hours on days -6 to -4, etoposide IV over 4 hours on day -4, and cyclophosphamide IV on
day -2. Patients undergo autologous peripheral blood stem cell transplantation on day
0.

Patients are followed at 60 days, every 3 months for 1 year, every 6 months for 2 years, and
then annually thereafter.

PROJECTED ACCRUAL: Approximately 460 patients will be accrued for this study within 4 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed stage III or IV Hodgkin's disease with at least 3 of the
following characteristics:

- Albumin less than 4.0 mg/dL

- Hemoglobin less than 10.5 g/dL

- Leukocytosis at least 15,000/mm^3

- Lymphocytopenia less than 600/mm^3 or less than 8% of total WBC

- Male sex

- At least 45 years of age

- Stage IV disease

- Bidimensionally measurable disease

- Bilateral or unilateral bone marrow aspiration and biopsy performed within 42 days of
study

- Negative chest x-ray within 42 days of study OR

- Chest x-ray performed within 28 days of study

- Negative CT scan of thorax, abdomen, and pelvis within 42 days of study OR

- CT scan of thorax, abdomen, and pelvis performed within 28 days of study

- No history of lymphoma, myelodyplastic syndrome, or leukemia

- No CNS involvement by Hodgkin's disease

PATIENT CHARACTERISTICS:

Age:

- 15 to 65

Performance status:

- Zubrod 0-1

Life expectancy:

- Not specified

Hematopoietic:

- See Disease Characteristics

Hepatic:

- See Disease Characteristics

- Bilirubin no greater than 1.5 times upper limit of normal (ULN) (unless elevation due
to liver infiltration by Hodgkin's disease)

- Lymphoma-related hepatic dysfunction allowed

Renal:

- Creatinine no greater than 2.0 times ULN

- Creatinine clearance at least 60 mL/min

- Lymphoma-related renal dysfunction allowed

Cardiovascular:

- No coronary artery disease, cardiomyopathy, congestive heart failure, or arrhythmias
requiring therapy

- Ejection fraction normal

- No significant EKG abnormalities suggesting active cardiac disease

Pulmonary:

- Corrected DLCO at least 60% OR

- FEV1 at least 60% predicted

Other:

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No HIV or AIDS

- No other prior malignancy within past 5 years except adequately treated basal cell or
squamous cell skin cancer

- No active bacterial, fungal, or viral infection*

- Afebrile for 3 consecutive days* NOTE: *Prior to randomization portion of study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- No prior chemotherapy for Hodgkin's disease except single course of ABVD
(doxorubicin, bleomycin, vinblastine, and dacarbazine) within 35 days of study

Endocrine therapy:

- Not specified

Radiotherapy:

- No prior radiotherapy for Hodgkin's disease

Surgery:

- Not specified

Other:

- At least 3 days since prior antibiotics, antifungals, or antivirals (except for
prophylactic therapy or fever associated with underlying lymphoma) (for randomization
portion of study)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Time Frame:

every 3 months while on protocol treatment, then every 6 months for 2 years, then annually thereafter

Safety Issue:

No

Principal Investigator

Ellen R. Gaynor, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Loyola University

Authority:

United States: Federal Government

Study ID:

CDR0000067708

NCT ID:

NCT00005090

Start Date:

April 2000

Completion Date:

May 2005

Related Keywords:

  • Lymphoma
  • stage III adult Hodgkin lymphoma
  • stage IV adult Hodgkin lymphoma
  • Hodgkin Disease
  • Lymphoma

Name

Location

Roswell Park Cancer Institute Buffalo, New York  14263
Memorial Sloan-Kettering Cancer Center New York, New York  10021
Walter Reed Army Medical Center Washington, District of Columbia  20307-5000
University of Chicago Cancer Research Center Chicago, Illinois  60637
University of Massachusetts Memorial Medical Center Worcester, Massachusetts  01655
University of Minnesota Cancer Center Minneapolis, Minnesota  55455
Lineberger Comprehensive Cancer Center, UNC Chapel Hill, North Carolina  27599-7295
Duke Comprehensive Cancer Center Durham, North Carolina  27710
Arthur G. James Cancer Hospital - Ohio State University Columbus, Ohio  43210
Rhode Island Hospital Providence, Rhode Island  02903
Vermont Cancer Center Burlington, Vermont  05401-3498
CCOP - Southern Nevada Cancer Research Foundation Las Vegas, Nevada  89106
University of California San Diego Cancer Center La Jolla, California  92093-0658
UCSF Cancer Center and Cancer Research Institute San Francisco, California  94115-0128
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
CCOP - Mount Sinai Medical Center Miami Beach, Florida  33140
Marlene & Stewart Greenebaum Cancer Center, University of Maryland Baltimore, Maryland  21201
Ellis Fischel Cancer Center - Columbia Columbia, Missouri  65203
Barnes-Jewish Hospital Saint Louis, Missouri  63110
Norris Cotton Cancer Center Lebanon, New Hampshire  03756
CCOP - North Shore University Hospital Manhasset, New York  11030
State University of New York - Upstate Medical University Syracuse, New York  13210
CCOP - Southeast Cancer Control Consortium Winston-Salem, North Carolina  27104-4241
University of Tennessee, Memphis Cancer Center Memphis, Tennessee  38103
MBCCOP - Massey Cancer Center Richmond, Virginia  23298-0037
Mount Sinai Medical Center, NY New York, New York  10029
New York Presbyterian Hospital - Cornell Campus New York, New York  10021
Holden Comprehensive Cancer Center at The University of Iowa Iowa City, Iowa  52242-1009
Comprehensive Cancer Center at Wake Forest University Winston-Salem, North Carolina  27157-1082
Lombardi Cancer Center Washington, District of Columbia  20007
Veterans Affairs Medical Center - Birmingham Birmingham, Alabama  35233
Green Mountain Oncology Group Rutland, Vermont  05701
Veterans Affairs Medical Center - White River Junction White River Junction, Vermont  05009
Dana-Farber Cancer Institute Boston, Massachusetts  02115
Veterans Affairs Medical Center - Chicago (Westside Hospital) Chicago, Illinois  60612
Veterans Affairs Medical Center - San Francisco San Francisco, California  94121
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. Syracuse, New York  13217
Veterans Affairs Medical Center - Memphis Memphis, Tennessee  38104
Veterans Affairs Medical Center - Richmond Richmond, Virginia  23249
Veterans Affairs Medical Center - Togus Togus, Maine  04330
Veterans Affairs Medical Center - Minneapolis Minneapolis, Minnesota  55417
Veterans Affairs Medical Center - Columbia (Truman Memorial) Columbia, Missouri  65201
University of Nebraska Medical Center Omaha, Nebraska  68198-3330
Veterans Affairs Medical Center - Buffalo Buffalo, New York  14215
Veterans Affairs Medical Center - Syracuse Syracuse, New York  13210
Veterans Affairs Medical Center - Durham Durham, North Carolina  27705
Schneider Children's Hospital at North Shore Manhasset, New York  11030