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

NCT00070187 | Completed Phase 2 DMC

• 3 other identifiers: AHOD0121CDR0000330135COG-AHOD0121
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 63

Brief 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. 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.

Conditions

Lymphoma

Keywords

recurrent adult Hodgkin lymphoma; recurrent/refractory childhood Hodgkin lymphoma

Outcome Measures

Primary Outcomes (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.

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

Study Arms (2)

Hyperfractionated Involved-Field Radiotion-immunotherapy

EXPERIMENTAL

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; 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 immunotherapy

EXPERIMENTAL

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; 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

Interventions

aldesleukin BIOLOGICAL

Given IV

Also known as: Proleukin, IL-2, recombinant human Interleukin 2, NSC # 373364

Hyperfractionated Involved-Field Radiotion-immunotherapy

filgrastim BIOLOGICAL

Given IV

Also known as: GRANULOCYTE COLONY-STIMULATING FACTOR, r-metHuG-CSF, G-CSF, Neupogen, NSC #614629

Hyperfractionated Involved-Field Radiotion-immunotherapy; Hyperfractionated Involved-Field Radiotion-no immunotherapy

recombinant interferon gamma BIOLOGICAL

Given IV

Also known as: INTERFERON GAMMA-1b, Actimmune, gamma interferon, immune interferon, lymphocyte interferon, rIFN-gamma, T-interferon, NSC #600662

Hyperfractionated Involved-Field Radiotion-immunotherapy

carmustine DRUG

Given IV

Also known as: BCNU, BiCNU, bischloronitrosourea, NSC #40996

Hyperfractionated Involved-Field Radiotion-immunotherapy; Hyperfractionated Involved-Field Radiotion-no immunotherapy

cyclosporine DRUG

Given IV

Also known as: cycloporine, Sandimmune, Neoral, Gengraf, NSC #290193

Hyperfractionated Involved-Field Radiotion-immunotherapy; Hyperfractionated Involved-Field Radiotion-no immunotherapy

cytarabine DRUG

Given IV

Also known as: cytosine arabinoside, AraC, Cytosar, NSC #063878

Hyperfractionated Involved-Field Radiotion-immunotherapy; Hyperfractionated Involved-Field Radiotion-no immunotherapy

etoposide DRUG

Given IV

Also known as: VP-16, VePesid, Etopophos, NSC #141540

Hyperfractionated Involved-Field Radiotion-immunotherapy; Hyperfractionated Involved-Field Radiotion-no immunotherapy

melphalan DRUG

Given IV

Also known as: L-PHENYLANINE mustard, L-PAM, L-sarcolysin, Alkeran, NSC #008806

Hyperfractionated Involved-Field Radiotion-immunotherapy; Hyperfractionated Involved-Field Radiotion-no immunotherapy

autologous bone marrow transplantation PROCEDURE

Hyperfractionated Involved-Field Radiotion-immunotherapy; Hyperfractionated Involved-Field Radiotion-no immunotherapy

bone marrow ablation with stem cell support PROCEDURE

Hyperfractionated Involved-Field Radiotion-immunotherapy; Hyperfractionated Involved-Field Radiotion-no immunotherapy

peripheral blood stem cell transplantation PROCEDURE

Hyperfractionated Involved-Field Radiotion-immunotherapy; Hyperfractionated Involved-Field Radiotion-no immunotherapy

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (63)

Comprehensive Cancer Center at University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016-7710, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

Children's Hospital and Research Center - Oakland

Oakland, California, 94609-1809, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Kaiser Permanente Medical Center - Oakland

Sacramento, California, 95825, United States

Location

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19899, United States

Location

Children's National Medical Center

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

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

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

Tampa, Florida, 33607, United States

Location

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, 33407, United States

Location

Emory University Hospital - Atlanta

Atlanta, Georgia, 30322, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62794-9620, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States

Location

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

Kansas City, Kansas, 66160-7357, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

Children's Hospital of New Orleans

New Orleans, Louisiana, 70118, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

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

Ann Arbor, Michigan, 48109-0238, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Spectrum Health Cancer Care - Butterworth Campus

Grand Rapids, Michigan, 49503-2560, United States

Location

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

Grosse Pointe Woods, Michigan, 48236, United States

Location

Children's Hospital of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Fairview University Medical Center - University Campus

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Long Island Cancer Center at Stony Brook University Hospital

Stony Brook, New York, 11794-8174, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106-5000, United States

Location

Children's Medical Center - Dayton

Dayton, Ohio, 45404-1815, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Tech University Health Sciences Center School of Medicine

Amarillo, Texas, 79106, United States

Location

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

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104-9958, United States

Location

Covenant Children's Hospital

Lubbock, Texas, 79410, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229-3993, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

Children's Hospital of the King's Daughters

Norfolk, Virginia, 23507-1971, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, 54449, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Conditions

Lymphoma; Hodgkin Disease; Recurrence

Interventions

aldesleukin; Interleukin-2; Filgrastim; Granulocyte Colony-Stimulating Factor; Interferon-gamma; interferon gamma-1b; interferon gamma, Cys(-3), Tyr(-2), Cys(-1)-; Carmustine; Cyclosporine; Cyclosporins; Cytarabine; Etoposide; etoposide phosphate; Melphalan; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Interferons; Macrophage-Activating Factors; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Glucosides; Glycosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Allen R. Chen, MD, PhD, MHS

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

• Sharon L. Gardner, MD

  NYU Langone Health

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2003
• First Posted: October 7, 2003
• Study Start: November 1, 2003
• Primary Completion: June 1, 2005
• Last Updated: October 17, 2013

Record last verified: 2013-10

Locations

CA (2); US (60); AU (1)