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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
30 Years
Not Enrolling

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Trial Information

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.

Inclusion Criteria


- Diagnosis of Hodgkin's lymphoma

- Histologically confirmed at original diagnosis AND at relapse or disease

- 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)



- Under 30

Performance status

- ECOG 0-2 (for adults)

- Lansky 50-100% (for children)

Life expectancy

- At least 2 months


- Absolute neutrophil count at least 500/mm^3


- Bilirubin no greater than 1.5 times normal

- SGPT less than 2.5 times normal


- 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


- Shortening fraction at least 27% by echocardiogram OR

- Ejection fraction at least 50% by MUGA


- No evidence of dyspnea at rest

- No exercise intolerance

- DLCO at least 50% (patients 8 years of age and over)


- Not pregnant or nursing

- Negative pregnancy test

- No concurrent serious illness


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


- 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


- See Disease Characteristics

- Recovered from prior radiotherapy


- Not specified


- No concurrent participation in another COG therapeutic study

Type of Study:


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:


Principal Investigator

Allen R. Chen, MD, PhD, MHS

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

November 2003

Completion Date:

Related Keywords:

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



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