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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.
Sponsors and Collaborators: Children's Oncology Group
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
Drug: filgrastim
Drug: indium In 111 ibritumomab tiuxetan
Drug: rituximab
Drug: yttrium Y 90 ibritumomab tiuxetan
Procedure: peripheral blood stem cell transplantation
Phase I

MedlinePlus related topics: Cancer Lymphoma
Drug Information available for: Filgrastim Rituximab Immunoglobulins Globulin, Immune Ibritumomab tiuxetan Indium in 111 oxyquinoline
U.S. FDA Resources
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

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

  Show 28 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Mitchell S. Cairo, MD Herbert Irving Comprehensive Cancer Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
Study ID Numbers: CDR0000069331, COG-ADVL0013
Study First Received: May 13, 2002
Last Updated: October 18, 2008
ClinicalTrials.gov Identifier: NCT00036855  
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

Study placed in the following topic categories:
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Hodgkin's disease
Rituximab
Lymphoblastic lymphoma
Small non-cleaved cell lymphoma
Recurrence
Central nervous system lymphoma, primary
Antibodies, Monoclonal
Lymphoma, large-cell
Lymphatic Diseases
Antibodies
Hodgkin lymphoma, childhood
Lymphoproliferative Disorders
Lymphoma
Hodgkin Disease
Immunoglobulins

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Immunologic Factors
Immune System Diseases
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Antirheumatic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009