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A Phase II/III Study of Immunomodulation After High Dose Myeloablative Therapy With Autologous Stem Cell Rescue for Refractory/Relapsed Hodgkin Disease


Phase 2/Phase 3
N/A
30 Years
Not Enrolling
Both
Lymphoma

Thank you

Trial Information

A Phase II/III Study of Immunomodulation After High Dose Myeloablative Therapy With Autologous Stem Cell Rescue for Refractory/Relapsed Hodgkin Disease


OBJECTIVES:

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 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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Incidence of death, excluding death due to disease, during the period of time from day 0 (transplant) through day 100 post transplant

Outcome Description:

Death, excluding death due to disease, during the period of time from Day 0 (transplant) through Day 100 post transplant.

Outcome Time Frame:

Day 0 (transplant) through Day 100 (Post transplant)

Safety Issue:

No

Principal Investigator

Allen R. Chen, MD, PhD, MHS

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

AHOD0121

NCT ID:

NCT00070187

Start Date:

November 2003

Completion Date:

Related Keywords:

  • Lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • Hodgkin Disease
  • Lymphoma

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Emory University Hospital - AtlantaAtlanta, Georgia  30322
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Hurley Medical CenterFlint, Michigan  48503
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
New York Medical CollegeValhalla, New York  10595
University of Miami Sylvester Comprehensive Cancer CenterMiami, Florida  33136
Long Island Cancer Center at Stony Brook University HospitalStony Brook, New York  11790-7775
CCOP - Scott and White HospitalTemple, Texas  76508
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Nemours Children's ClinicJacksonville, Florida  32207
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Children's Hospital of New OrleansNew Orleans, Louisiana  70118
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Southern Illinois University School of MedicineSpringfield, Illinois  62794-9658
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Children's Medical Center - DaytonDayton, Ohio  45404
Texas Tech University Health Sciences Center School of MedicineAmarillo, Texas  79106
Covenant Children's HospitalLubbock, Texas  79410
Children's Hospital of the King's DaughtersNorfolk, Virginia  23507
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Fairview University Medical Center - University CampusMinneapolis, Minnesota  55455
Comprehensive Cancer Center at University of Alabama at BirminghamBirmingham, Alabama  35294
Children's Hospital and Research Center - OaklandOakland, California  94609-1809
Kaiser Permanente Medical Center - OaklandSacramento, California  95825
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
Kaplan Cancer Center at St. Mary's Medical CenterWest Palm Beach, Florida  33407
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
C.S. Mott Children's Hospital at University of MichiganAnn Arbor, Michigan  48109-0238
Spectrum Health Cancer Care - Butterworth CampusGrand Rapids, Michigan  49503-2560
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
Mount Sinai Medical CenterNew York, New York  10029
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
Children's Hospital of Minnesota - MinneapolisMinneapolis, Minnesota  55404