A Phase II/III Study of Immunomodulation After High Dose Myeloablative Therapy With Autologous Stem Cell Rescue for Refractory/Relapsed Hodgkin Disease
- 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 III
- Compare the event-free and overall survival of patients treated with vs without
this immunotherapy regimen.
- 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
- Determine the effectiveness of this immunotherapy regimen in producing autologous
graft-vs-host disease (GVHD) and auto-reactive cytotoxic T-lymphocyte activity in these
- 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
- 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
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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of death, excluding death due to disease, during the period of time from day 0 (transplant) through day 100 post transplant
Death, excluding death due to disease, during the period of time from Day 0 (transplant) through Day 100 post transplant.
Day 0 (transplant) through Day 100 (Post transplant)
Allen R. Chen, MD, PhD, MHS
Sidney Kimmel Comprehensive Cancer Center
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|
|Emory University Hospital - Atlanta||Atlanta, Georgia 30322|
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|
|University of Mississippi Medical Center||Jackson, Mississippi 39216-4505|
|Hurley Medical Center||Flint, Michigan 48503|
|University of Texas Health Science Center at San Antonio||San Antonio, Texas 78284-7811|
|Midwest Children's Cancer Center||Milwaukee, Wisconsin 53226|
|Van Elslander Cancer Center at St. John Hospital and Medical Center||Grosse Pointe Woods, Michigan 48236|
|Penn State Cancer Institute at Milton S. Hershey Medical Center||Hershey, Pennsylvania 17033-0850|
|Marshfield Clinic - Marshfield Center||Marshfield, Wisconsin 54449|
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|New York Medical College||Valhalla, New York 10595|
|University of Miami Sylvester Comprehensive Cancer Center||Miami, Florida 33136|
|Long Island Cancer Center at Stony Brook University Hospital||Stony Brook, New York 11790-7775|
|CCOP - Scott and White Hospital||Temple, Texas 76508|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|Children's Hospital of Orange County||Orange, California 92668|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Mercy Hospital||Kansas City, Missouri 64108|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Nemours Children's Clinic||Jacksonville, Florida 32207|
|Miami Children's Hospital||Miami, Florida 33155-4069|
|All Children's Hospital||St. Petersburg, Florida 33701|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|Children's Hospital of New Orleans||New Orleans, Louisiana 70118|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Cook Children's Medical Center - Fort Worth||Fort Worth, Texas 76104|
|Phoenix Children's Hospital||Phoenix, Arizona 85016-7710|
|Southern Illinois University School of Medicine||Springfield, Illinois 62794-9658|
|Kosair Children's Hospital||Louisville, Kentucky 40202-3830|
|Children's Medical Center - Dayton||Dayton, Ohio 45404|
|Texas Tech University Health Sciences Center School of Medicine||Amarillo, Texas 79106|
|Covenant Children's Hospital||Lubbock, Texas 79410|
|Children's Hospital of the King's Daughters||Norfolk, Virginia 23507|
|Arkansas Cancer Research Center at University of Arkansas for Medical Sciences||Little Rock, Arkansas 72205|
|Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center||Kansas City, Kansas 66160-7353|
|Fairview University Medical Center - University Campus||Minneapolis, Minnesota 55455|
|Comprehensive Cancer Center at University of Alabama at Birmingham||Birmingham, Alabama 35294|
|Children's Hospital and Research Center - Oakland||Oakland, California 94609-1809|
|Kaiser Permanente Medical Center - Oakland||Sacramento, California 95825|
|University of Florida Shands Cancer Center||Gainesville, Florida 32610-0232|
|St. Joseph's Cancer Institute at St. Joseph's Hospital||Tampa, Florida 33607|
|Kaplan Cancer Center at St. Mary's Medical Center||West Palm Beach, Florida 33407|
|St. Vincent Indianapolis Hospital||Indianapolis, Indiana 46260|
|C.S. Mott Children's Hospital at University of Michigan||Ann Arbor, Michigan 48109-0238|
|Spectrum Health Cancer Care - Butterworth Campus||Grand Rapids, Michigan 49503-2560|
|Hackensack University Medical Center Cancer Center||Hackensack, New Jersey 07601|
|Mount Sinai Medical Center||New York, New York 10029|
|SUNY Upstate Medical University Hospital||Syracuse, New York 13210|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Rainbow Babies and Children's Hospital||Cleveland, Ohio 44106-5000|
|Hollings Cancer Center at Medical University of South Carolina||Charleston, South Carolina 29425|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas||Dallas, Texas 75390|
|Methodist Children's Hospital of South Texas||San Antonio, Texas 78229-3993|
|St. Vincent Hospital Regional Cancer Center||Green Bay, Wisconsin 54307-3508|
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|
|Alfred I. duPont Hospital for Children||Wilmington, Delaware 19803|
|Children's Hospital of Minnesota - Minneapolis||Minneapolis, Minnesota 55404|