Immunotherapy Using Cyclosporine, Interferon Gamma, and Interleukin-2 After High-Dose Myeloablative Chemotherapy With Autologous Stem Cell Transplantation in Treating Patients With Refractory or Relapsed Hodgkin's Lymphoma
NCT ID: NCT00070187
Last Updated: 2013-10-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2/PHASE3
24 participants
INTERVENTIONAL
2003-11-30
Brief Summary
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PURPOSE: This randomized phase II/III trial is studying how well high-dose chemotherapy followed by autologous stem cell transplantation, cyclosporine, interferon gamma, and interleukin-2 works and compares it to high-dose chemotherapy followed by autologous stem cell transplantation only in treating patients with refractory or relapsed Hodgkin's lymphoma.
Detailed Description
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Primary
* Phase II
* Determine the feasibility and toxicity of immunotherapy comprising cyclosporine, interferon gamma, and interleukin-2 after high-dose myeloablative chemotherapy with autologous stem cell transplantation (ASCT) in patients with refractory or relapsed Hodgkin's lymphoma.
* Phase II part of the study was completed and should have proceeded to Phase III; however long delay occurred due to some proposed protocol changes to Phase III , so long that the study got permanently closed \*\*\*\*\*\*\*\*\*\*\*
* Phase III
* Compare the event-free and overall survival of patients treated with vs without this immunotherapy regimen.
Secondary
* Determine the event-free and overall survival rates, toxic effects, and response rates to reinduction chemotherapy followed by hyperfractionated involved-field radiotherapy, high-dose chemotherapy comprising carmustine, etoposide, cytarabine, and melphalan, and ASCT in these patients.
* Correlate tumor biologic characteristics with response in patients treated with these regimens.
* Determine the effectiveness of this immunotherapy regimen in producing autologous graft-vs-host disease (GVHD) and auto-reactive cytotoxic T-lymphocyte activity in these patients.
* Correlate greater levels of autologous GVHD and in vitro cytolytic activity with improved event-free and overall survival in patients treated with these regimens.
* Determine whether treatment with immunotherapy can overcome the negative prognostic significance of p53 mutation and high serum levels of interleukin-10 and interleukin-2 receptor in these patients.
* Determine the genotoxicity of retrieval therapy and the incidence of hypermutability by longitudinal genotoxic biomonitoring in these patients.
* Correlate HLA class II invariant peptide (CLIP) expression in tumor cells with improved event-free and overall survival in patients treated with immunotherapy regimen.
OUTLINE: This is a nonrandomized, multicenter phase II study followed by a randomized, multicenter phase III study. Patients are stratified according to study phase (II vs III).
Patients receive 2 courses of salvage induction therapy on COG-AHOD00P1 or equivalent. Within 2-5 weeks after completion of salvage induction therapy, patients receive protocol therapy.
* Phase II: All patients receive the following treatment:
* Hyperfractionated involved-field radiotherapy: Patients who have completed prior salvage induction therapy and have not received full tissue tolerance from prior radiotherapy may receive hyperfractionated involved-field radiotherapy twice daily for 7 days.
* High-dose preparative regimen: Beginning within 7 days after radiotherapy, patients receive carmustine IV over 3 hours on day -6; etoposide IV over 1 hour and cytarabine IV over 1 hour on days -5 to -2; and melphalan IV over 30 minutes on day -1.
* Autologous stem cell transplantation: Patients undergo autologous bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive filgrastim (G-CSF) subcutaneously (SC) or IV beginning on day 1 and continuing until blood counts recover.
* Immunotherapy: Patients receive cyclosporine IV twice daily beginning on day 0 and continuing until the completion of the course of interferon gamma and interleukin-2. When sufficiently recovered, patients also receive interferon gamma SC every other day for 10 doses. Beginning 2 days after the start of interferon gamma, patients also receive interleukin-2 SC once daily for 18 days.
* Phase III: Patients who respond to prior salvage induction therapy are randomized to 1 of 2 treatment arms. Patients who have progressive disease after 2 courses of prior salvage induction therapy are assigned to arm I.
* Arm I: Patients receive treatment as in phase II.
* Arm II: Patients receive treatment as in phase II without immunotherapy. In both phases, treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed at 1 year.
PROJECTED ACCRUAL: A total of 156 patients (25 for phase II and 131 for phase III) will be accrued for this study within 5.4 years.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Hyperfractionated Involved-Field Radiotion-immunotherapy
Completed prior salvage induction therapy and have not received full tissue tolerance from prior radiotherapy may receive hyperfractionated involved-field radiotherapy twice daily for 7 days.
HIGH-DOSE PREPARATIVE REGIMEN: Beginning within 7 days after radiotherapy, carmustine IV over 3 hours on day -6; etoposide IV over 1 hour and cytarabine IV over 1 hour on days -5 to -2; and melphalan IV over 30 minutes on day -1.
ASCT: Autologous bone marrow or peripheral blood stem cell transplantation on day 0. Filgrastim (oral or IV) beginning on day 1 and continuing until blood counts recover.
IMMUNOTHERAPY: Cyclosporine IV twice daily beginning on day 0 and continuing until the completion of the course of recombinant interferon gamma and interleukin-2. When sufficiently recovered, Aldesleukin once daily for 18 days.
aldesleukin
Given IV
filgrastim
Given IV
recombinant interferon gamma
Given IV
carmustine
Given IV
cyclosporine
Given IV
cytarabine
Given IV
etoposide
Given IV
melphalan
Given IV
autologous bone marrow transplantation
bone marrow ablation with stem cell support
peripheral blood stem cell transplantation
Hyperfractionated Involved-Field Radiotion-no immunotherapy
Completed prior salvage induction therapy and have not received full tissue tolerance from prior radiotherapy may receive hyperfractionated involved-field radiotherapy twice daily for 7 days.
HIGH-DOSE PREPARATIVE REGIMEN: Beginning within 7 days after radiotherapy, carmustine IV over 3 hours on day -6; etoposide IV over 1 hour and cytarabine IV over 1 hour on days -5 to -2; and melphalan IV over 30 minutes on day -1.
ASCT: Autologous bone marrow or peripheral blood stem cell transplantation on day 0. Filgrastim (oral or IV) beginning on day 1 and continuing until blood counts recover.
filgrastim
Given IV
carmustine
Given IV
cyclosporine
Given IV
cytarabine
Given IV
etoposide
Given IV
melphalan
Given IV
autologous bone marrow transplantation
bone marrow ablation with stem cell support
peripheral blood stem cell transplantation
Interventions
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aldesleukin
Given IV
filgrastim
Given IV
recombinant interferon gamma
Given IV
carmustine
Given IV
cyclosporine
Given IV
cytarabine
Given IV
etoposide
Given IV
melphalan
Given IV
autologous bone marrow transplantation
bone marrow ablation with stem cell support
peripheral blood stem cell transplantation
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Diagnosis of Hodgkin's lymphoma
* Histologically confirmed at original diagnosis AND at relapse or disease progression
* Relapsed or refractory to conventional therapy
* No recurrence without B symptoms or bulky disease at least 1 year after completion of minimal systemic therapy defined by either of the following:
* Stage IA/IIA with nodal disease previously treated with radiotherapy only
* Stage IA/IIA with nodal disease previously treated with less than 3 courses of standard dose chemotherapy
* Concurrently enrolled on the COG-AHOD00P1 salvage chemotherapy study OR received other appropriate salvage therapy (e.g., ifosfamide and vinorelbine)
PATIENT CHARACTERISTICS:
Age
* Under 30
Performance status
* ECOG 0-2 (for adults)
* Lansky 50-100% (for children)
Life expectancy
* At least 2 months
Hematopoietic
* Absolute neutrophil count at least 500/mm\^3
Hepatic
* Bilirubin no greater than 1.5 times normal
* SGPT less than 2.5 times normal
Renal
* Creatinine no greater than 1.5 times normal OR
* Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min/1.73 m\^2
Cardiovascular
* Shortening fraction at least 27% by echocardiogram OR
* Ejection fraction at least 50% by MUGA
Pulmonary
* No evidence of dyspnea at rest
* No exercise intolerance
* DLCO at least 50% (patients 8 years of age and over)
Other
* Not pregnant or nursing
* Negative pregnancy test
* No concurrent serious illness
PRIOR CONCURRENT THERAPY:
Biologic therapy
* Recovered from prior immunotherapy
* At least 1 week since prior antineoplastic biologic agents
* More than 1 week since prior growth factors
* No prior stem cell transplantation
* No other concurrent immunomodulating agents
Chemotherapy
* See Disease Characteristics
* More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
* No other concurrent anticancer chemotherapy
Endocrine therapy
* No concurrent steroids, including dexamethasone as an antiemetic
Radiotherapy
* See Disease Characteristics
* Recovered from prior radiotherapy
Surgery
* Not specified
Other
* No concurrent participation in another COG therapeutic study
30 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Children's Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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Allen R. Chen, MD, PhD, MHS
Role: STUDY_CHAIR
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sharon L. Gardner, MD
Role: STUDY_CHAIR
NYU Langone Health
Locations
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Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States
Children's Hospital and Research Center - Oakland
Oakland, California, United States
Children's Hospital of Orange County
Orange, California, United States
Kaiser Permanente Medical Center - Oakland
Sacramento, California, United States
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Florida Shands Cancer Center
Gainesville, Florida, United States
Nemours Children's Clinic
Jacksonville, Florida, United States
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Miami Children's Hospital
Miami, Florida, United States
All Children's Hospital
St. Petersburg, Florida, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States
Emory University Hospital - Atlanta
Atlanta, Georgia, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Indiana University Cancer Center
Indianapolis, Indiana, United States
St. Vincent Indianapolis Hospital
Indianapolis, Indiana, United States
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States
Kosair Children's Hospital
Louisville, Kentucky, United States
Children's Hospital of New Orleans
New Orleans, Louisiana, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
C.S. Mott Children's Hospital at University of Michigan
Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Hurley Medical Center
Flint, Michigan, United States
Spectrum Health Cancer Care - Butterworth Campus
Grand Rapids, Michigan, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States
Children's Hospital of Minnesota - Minneapolis
Minneapolis, Minnesota, United States
Fairview University Medical Center - University Campus
Minneapolis, Minnesota, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Mount Sinai Medical Center
New York, New York, United States
Long Island Cancer Center at Stony Brook University Hospital
Stony Brook, New York, United States
SUNY Upstate Medical University Hospital
Syracuse, New York, United States
New York Medical College
Valhalla, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States
Children's Medical Center - Dayton
Dayton, Ohio, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Texas Tech University Health Sciences Center School of Medicine
Amarillo, Texas, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States
Covenant Children's Hospital
Lubbock, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
CCOP - Scott and White Hospital
Temple, Texas, United States
Children's Hospital of the King's Daughters
Norfolk, Virginia, United States
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
Hopital Sainte Justine
Montreal, Quebec, Canada
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada
Countries
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References
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Chen AR, Hutchison R, Hess A, et al.: Clinical outcomes of patients with recurrent/refractory Hodgkin disease receiving cyclosporine, interferon-, and interleukin-2 immunotherapy to induce auto-reactivity after autologous stem cell transplantation with BEAM: a COG study. [Abstract] Blood 110 (11): A-1896, 2007.
Other Identifiers
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CDR0000330135
Identifier Type: OTHER
Identifier Source: secondary_id
COG-AHOD0121
Identifier Type: OTHER
Identifier Source: secondary_id
AHOD0121
Identifier Type: -
Identifier Source: org_study_id