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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00070187
First received: October 3, 2003
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Giving immunotherapy using cyclosporine, interferon gamma, and interleukin-2 after stem cell transplantation may help the transplanted cells make an immune response and kill any remaining cancer cells. It is not yet known whether high-dose chemotherapy followed by autologous stem cell transplantation is more effective with or without immunotherapy.

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.


Condition Intervention Phase
Lymphoma
Biological: aldesleukin
Biological: filgrastim
Biological: recombinant interferon gamma
Drug: carmustine
Drug: cyclosporine
Drug: cytarabine
Drug: etoposide
Drug: melphalan
Procedure: autologous bone marrow transplantation
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II/III Study of Immunomodulation After High Dose Myeloablative Therapy With Autologous Stem Cell Rescue for Refractory/Relapsed Hodgkin Disease

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Incidence of death, excluding death due to disease, during the period of time from day 0 (transplant) through day 100 post transplant [ Time Frame: Day 0 (transplant) through Day 100 (Post transplant) ] [ Designated as safety issue: Yes ]
    Death, excluding death due to disease, during the period of time from Day 0 (transplant) through Day 100 post transplant.


Enrollment: 24
Study Start Date: November 2003
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Biological: aldesleukin
Given IV
Other Names:
  • Proleukin
  • IL-2
  • recombinant human Interleukin 2
  • NSC # 373364
Biological: filgrastim
Given IV
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Filgrastim
  • Neupogen
  • NSC #614629
Biological: recombinant interferon gamma
Given IV
Other Names:
  • INTERFERON GAMMA-1b
  • Actimmune
  • gamma interferon
  • immune interferon
  • lymphocyte interferon
  • rIFN-gamma
  • T-interferon
  • NSC #600662
Drug: carmustine
Given IV
Other Names:
  • BCNU
  • BiCNU
  • bischloronitrosourea
  • NSC #40996
Drug: cyclosporine
Given IV
Other Names:
  • cycloporine
  • Sandimmune
  • Neoral
  • Gengraf
  • NSC #290193
Drug: cytarabine
Given IV
Other Names:
  • cytosine arabinoside
  • AraC
  • Cytosar
  • NSC #063878
Drug: etoposide
Given IV
Other Names:
  • VP-16
  • VePesid
  • Etopophos
  • NSC #141540
Drug: melphalan
Given IV
Other Names:
  • L-PHENYLANINE mustard
  • L-PAM
  • L-sarcolysin
  • Alkeran
  • NSC #008806
Procedure: autologous bone marrow transplantation Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation
Experimental: 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.

Biological: filgrastim
Given IV
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Filgrastim
  • Neupogen
  • NSC #614629
Drug: carmustine
Given IV
Other Names:
  • BCNU
  • BiCNU
  • bischloronitrosourea
  • NSC #40996
Drug: cyclosporine
Given IV
Other Names:
  • cycloporine
  • Sandimmune
  • Neoral
  • Gengraf
  • NSC #290193
Drug: cytarabine
Given IV
Other Names:
  • cytosine arabinoside
  • AraC
  • Cytosar
  • NSC #063878
Drug: etoposide
Given IV
Other Names:
  • VP-16
  • VePesid
  • Etopophos
  • NSC #141540
Drug: melphalan
Given IV
Other Names:
  • L-PHENYLANINE mustard
  • L-PAM
  • L-sarcolysin
  • Alkeran
  • NSC #008806
Procedure: autologous bone marrow transplantation Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070187

  Show 63 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Allen R. Chen, MD, PhD, MHS Sidney Kimmel Comprehensive Cancer Center
Study Chair: Sharon L. Gardner, MD New York University School of Medicine
  More Information

Additional Information:
Publications:
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.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00070187     History of Changes
Other Study ID Numbers: AHOD0121, CDR0000330135, COG-AHOD0121
Study First Received: October 3, 2003
Last Updated: October 16, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Aldesleukin
Carmustine
Cyclosporine
Cyclosporins
Cytarabine
Etoposide
Etoposide phosphate
Interferon-gamma
Interferons
Interleukin-2
Lenograstim
Melphalan
Adjuvants, Immunologic
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on October 20, 2014