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LymphomaPhase 2/3NCT00070187

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

A Phase 2/3 study testing aldesleukin, filgrastim and recombinant interferon gamma in people with Lymphoma, run by Children's Oncology Group at 63 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages Up to 30 years
Conditions the study is for
Lymphoma
What is being tested?
aldesleukin, filgrastim and recombinant interferon gamma
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
63 sitesin 3 countries
Study dates
Nov 2003to Jun 2005
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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

Trial locations and contacts

63 sites in 3 countries.

63 sites in 3 countries

United States60 sites

  • Texas Tech University Health Sciences Center School of Medicine

    Amarillo, Texas, 79106

  • C.S. Mott Children's Hospital at University of Michigan

    Ann Arbor, Michigan, 48109-0238

  • Emory University Hospital - Atlanta

    Atlanta, Georgia, 30322

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

  • Comprehensive Cancer Center at University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Hollings Cancer Center at Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Rainbow Babies and Children's Hospital

    Cleveland, Ohio, 44106-5000

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

  • Children's Medical Center - Dayton

    Dayton, Ohio, 45404-1815

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Cook Children's Medical Center - Fort Worth

    Fort Worth, Texas, 76104-9958

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • Spectrum Health Cancer Care - Butterworth Campus

    Grand Rapids, Michigan, 49503-2560

  • St. Vincent Hospital Regional Cancer Center

    Green Bay, Wisconsin, 54307-3508

  • Van Elslander Cancer Center at St. John Hospital and Medical Center

    Grosse Pointe Woods, Michigan, 48236

  • Hackensack University Medical Center Cancer Center

    Hackensack, New Jersey, 07601

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Indiana University Cancer Center

    Indianapolis, Indiana, 46202-5289

  • St. Vincent Indianapolis Hospital

    Indianapolis, Indiana, 46260

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216-4505

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

    Kansas City, Kansas, 66160-7357

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Jonsson Comprehensive Cancer Center at UCLA

    Los Angeles, California, 90095-1781

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • Covenant Children's Hospital

    Lubbock, Texas, 79410

  • Marshfield Clinic - Marshfield Center

    Marshfield, Wisconsin, 54449

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Miami Children's Hospital

    Miami, Florida, 33155

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • Children's Hospital of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • Fairview University Medical Center - University Campus

    Minneapolis, Minnesota, 55455

  • Children's Hospital of New Orleans

    New Orleans, Louisiana, 70118

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Children's Hospital of the King's Daughters

    Norfolk, Virginia, 23507-1971

  • Children's Hospital and Research Center - Oakland

    Oakland, California, 94609-1809

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016-7710

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Kaiser Permanente Medical Center - Oakland

    Sacramento, California, 95825

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229-3900

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229-3993

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62794-9620

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • Long Island Cancer Center at Stony Brook University Hospital

    Stony Brook, New York, 11794-8174

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • St. Joseph's Cancer Institute at St. Joseph's Hospital

    Tampa, Florida, 33607

  • CCOP - Scott and White Hospital

    Temple, Texas, 76508

  • New York Medical College

    Valhalla, New York, 10595

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010-2970

  • Kaplan Cancer Center at St. Mary's Medical Center

    West Palm Beach, Florida, 33407

  • Alfred I. duPont Hospital for Children

    Wilmington, Delaware, 19899

Other trials in United States

Canada2 sites

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Saskatoon Cancer Centre at the University of Saskatchewan

    Saskatoon, Saskatchewan, S7N 4H4

Other trials in Canada

Australia1 site

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

Other trials in Australia

About this study

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

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.

Read the detailed description

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 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
Lymphoma
Being tested
aldesleukin, filgrastim, recombinant interferon gamma, carmustine, cyclosporine
Keywords
recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma
Medical subject headings
Lymphoma, Hodgkin Disease, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • aldesleukinBiological

    Also called Proleukin, IL-2, recombinant human Interleukin 2, NSC # 373364

    Given IV

  • filgrastimBiological

    Also called GRANULOCYTE COLONY-STIMULATING FACTOR, r-metHuG-CSF, G-CSF, Neupogen

    Given IV

  • recombinant interferon gammaBiological

    Also called INTERFERON GAMMA-1b, Actimmune, gamma interferon, immune interferon

    Given IV

  • carmustineDrug

    Also called BCNU, BiCNU, bischloronitrosourea, NSC #40996

    Given IV

  • cyclosporineDrug

    Also called cycloporine, Sandimmune, Neoral, Gengraf

    Given IV

  • cytarabineDrug

    Also called cytosine arabinoside, AraC, Cytosar, NSC #063878

    Given IV

  • etoposideDrug

    Also called VP-16, VePesid, Etopophos, NSC #141540

    Given IV

  • melphalanDrug

    Also called L-PHENYLANINE mustard, L-PAM, L-sarcolysin, Alkeran

    Given IV

  • autologous bone marrow transplantationProcedure or surgery

  • bone marrow ablation with stem cell supportProcedure or surgery

  • peripheral blood stem cell transplantationProcedure or surgery

Study groups in NCT00070187
Study groupRoleWhat they receive
Hyperfractionated Involved-Field Radiotion-immunotherapyExperimentalCompleted 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.
Receives: 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
Hyperfractionated Involved-Field Radiotion-no immunotherapyExperimentalCompleted 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.
Receives: Biological: filgrastim; 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2003 (estimated)
  2. Study startNov 2003
  3. Primary completionJun 2005

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00070187
Sponsor's protocol ID
AHOD0121
Other IDs
CDR0000330135, COG-AHOD0121
Status last verified
Oct 2013
First submitted
3 Oct 2003
Last updated
17 Oct 2013
Results posted
No
Data monitoring committee
Yes

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.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing aldesleukin, filgrastim and recombinant interferon gamma in people with Lymphoma, run by Children's Oncology Group at 63 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 63 sites in United States, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00070187, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2013.

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