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Radiolabeled Monoclonal Antibody With or Without Peripheral Stem Cell Transplantation in Treating Children With Recurrent or Refractory Lymphoma
This study has been completed.
First Received: May 13, 2002   Last Updated: February 6, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00036855
  Purpose

RATIONALE: Radiolabeled monoclonal antibodies can locate cancer cells and deliver radioactive tumor-killing substances to them without harming normal cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by anticancer therapy.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy with or without peripheral stem cell transplantation in treating patients who have recurrent or refractory lymphoma.


Condition Intervention Phase
Lymphoma
Lymphoproliferative Disorder
Biological: filgrastim
Biological: rituximab
Procedure: peripheral blood stem cell transplantation
Radiation: indium In 111 ibritumomab tiuxetan
Radiation: yttrium Y 90 ibritumomab tiuxetan
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study Of Yttrium-Ibritumomab Tiuxetan (90Y Zevalin, Yttrium (90)-Anti-CD20, NSC # 710085) Preceded By Rituximab In Children With Recurrent/Refractory CD20 Positive Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: June 2002
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose (MTD) of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8) when preceded by rituximab in children with recurrent or refractory CD20-positive lymphoma for which no autologous peripheral blood stem cell transplantation (AuPBSCT) is planned. (Group A)
  • If the dose-limiting toxicity (DLT) in group A is purely hematological, determine the MTD of IDEC-Y2B8 when combined with rituximab, AuPBSCT, and filgrastim (G-CSF) in a second group of children with recurrent or refractory CD20-positive lymphoma. (Group B)
  • Determine the DLT of rituximab and IDEC-Y2B8 in these patients.
  • Determine the dosimetry of indium In 111 ibritumomab tiuxetan preceded by rituximab in these patients.
  • Determine, preliminarily, the antitumor activity of rituximab and IDEC-Y2B8 in these patients.
  • Assess the immune cell depletion (B-cell and T-cell) and recovery in patients treated with this regimen.
  • Determine the human anti-mouse antibody response in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8). Patients are assigned to 1 of 2 groups.

  • Group A (no planned peripheral blood stem cell [PBSC] support): Patients receive rituximab IV over 4-6 hours followed by indium In 111 ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0 and undergo whole body imaging. Patients may then receive rituximab IV over 4-6 hours followed by IDEC-Y2B8 IV over 10 minutes on day 7.

Cohorts of 3-6 patients in each subgroup (A1, A2, and A3) receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined (subgroup A1 closed as of 10/8/04). The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT).

Some patients receive autologous PBSC IV over 30-60 minutes on day 35.

  • Group B (planned PBSC support): Patients receive rituximab, IDEC-In2B8, and IDEC-Y2B8 as in group A. Patients also receive autologous PBSC IV over 30-60 minutes on day 21 and filgrastim (G-CSF) subcutaneously beginning on day 22 and continuing until blood counts recover or day 35.

If the DLT in group A is purely hematological, cohorts of 3-6 patients in group B receive escalating doses of IDEC-Y2B8 until the MTD is determined. The MTD is defined as in group A.

Patients in both groups are followed at days 63, 90, 180, 365, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 6-36 patients (6-24 for group A and 3-12 for group B) will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed and immunophenotypically (CD20)-positive lymphoma at original diagnosis, progression, or relapse
  • Refractory to conventional therapy

    • First recurrent/refractory CD20-positive non-Hodgkin's lymphoma (NHL) allowed if ineligible for or refused regimens with known curative potential (high-dose chemotherapy plus bone marrow transplantation) (if available)
    • Second or third progression and/or recurrence of NHL
    • Second or third relapse/refractory CD20-positive Hodgkin's lymphoma
    • CD20-positive, post-transplantation lymphoproliferative lymphoma that is medically refractory (decreased immunosuppression) to rituximab and/or chemotherapy
    • Medically refractory, HIV-associated, CD20-positive NHL
    • Recurrent/refractory CD20-positive lymphoblastic lymphoma
  • Autologous peripheral blood stem cells (PBSC) collected, selected for a minimum of 2 x 10^6 CD34-positive cells per kg, and cryopreserved before study entry
  • Meets one of the following criteria for bone marrow reserve:

    • Good marrow reserve, defined by both of the following:

      • No prior myeloablative stem cell transplantation (SCT)
      • No prior extensive radiotherapy, defined by any of the following:

        • Prior total body irradiation
        • Prior radiotherapy dose of 3,600 cGy or more to cranio-spinal axis
        • Prior radiotherapy to 50% or more of bone marrow
    • Poor marrow reserve, defined by either or both of the following:

      • Prior myeloablative SCT
      • Prior extensive radiotherapy

PATIENT CHARACTERISTICS:

Age:

  • Under 22

Performance status:

  • Lansky 50-100% (age 10 and under)
  • Karnofsky 50-100% (age 11 to 21)

Life expectancy:

  • At least 2 months

Hematopoietic:

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3 for patients with poor marrow reserve (transfusion independent)
  • Platelet count ≥ 150,000 for patients with good marrow reserve (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL (transfusion allowed)

Hepatic:

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 5 times ULN
  • Albumin ≥ 2 g/dL

Renal:

  • Creatinine normal OR
  • Creatinine clearance or glomerular filtration rate ≥ 70 mL/min

Cardiovascular:

  • Shortening fraction ≥ 27% by echocardiogram OR
  • Ejection fraction ≥ 50% by MUGA

Pulmonary:

  • No dyspnea at rest
  • No exercise intolerance
  • Oxygen saturation (SpO_2) > 94% by pulse oximetry (if there is a clinical indication for SpO_2 assessment)

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • No documented infection that is unresponsive to appropriate antibiotic, antiviral, or antifungal therapy
  • No grade 2 or greater CNS toxicity
  • Seizure disorder allowed if well controlled and on anticonvulsants

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics
  • Recovered from prior immunotherapy
  • At least 1 week since prior antineoplastic biologic agents
  • Prior SCT allowed if the following criteria are met:

    • At least 60 days since prior SCT
    • Full hematopoietic reconstitution post-SCT
  • No evidence of active acute or chronic graft-versus-host disease if post- allogeneic SCT
  • No concurrent sargramostim (GM-CSF)

Chemotherapy:

  • See Disease Characteristics
  • At least 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea) and recovered

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics
  • Recovered from prior radiotherapy

Surgery:

  • Not specified

Other:

  • No concurrent medications that would interact with the study drug
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00036855

  Hide Study Locations
Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States, 94304
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2916
United States, Georgia
MBCCOP-Medical College of Georgia Cancer Center
Augusta, Georgia, United States, 30912-4000
United States, Indiana
Riley Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, United States, 46202-5225
United States, Louisiana
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-2899
United States, Oregon
CCOP - Columbia River Oncology Program
Portland, Oregon, United States, 97225
Doernbecher Children's Hospital at Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
MBCCOP - South Texas Pediatrics
San Antonio, Texas, United States, 78229-3900
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390-9063
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
United States, Wisconsin
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Mitchell S. Cairo, MD Herbert Irving Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000069331, COG-ADVL0013
Study First Received: May 13, 2002
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00036855     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood lymphoblastic lymphoma
recurrent/refractory childhood Hodgkin lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
post-transplant lymphoproliferative disorder

Additional relevant MeSH terms:
Disease
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Rituximab
Physiological Effects of Drugs
Pharmacologic Actions
Antibodies, Monoclonal
Lymphatic Diseases
Neoplasms
Pathologic Processes
Therapeutic Uses
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma

ClinicalTrials.gov processed this record on November 27, 2009