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Radiolabeled Monoclonal Antibody With or Without Peripheral Stem Cell Transplantation in Treating Children With Recurrent or Refractory Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00036855
Recruitment Status : Terminated (Administratively complete.)
First Posted : January 27, 2003
Last Update Posted : January 17, 2013
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE May 13, 2002
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date January 17, 2013
Study Start Date  ICMJE June 2002
Actual Primary Completion Date March 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2013)
MTD, defined as that dose at which fewer than one-third of patients experience DLT graded according to the NCI CTC v 2.0 [ Time Frame: Up to day 49 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Radiolabeled Monoclonal Antibody With or Without Peripheral Stem Cell Transplantation in Treating Children With Recurrent or Refractory Lymphoma
Official Title  ICMJE 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
Brief Summary 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. 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
Detailed Description

OBJECTIVES:

I. 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) II. Determine the DLT of rituximab and IDEC-Y2B8 in these patients. III. Determine the dosimetry of indium In 111 ibritumomab tiuxetan preceded by rituximab in these patients.

IV. Determine, preliminarily, the antitumor activity of rituximab and IDEC-Y2B8 in these patients.

V. Assess the immune cell depletion (B-cell and T-cell) and recovery in patients treated with this regimen.

VI. 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • AIDS-related Peripheral/Systemic Lymphoma
  • AIDS-related Primary CNS Lymphoma
  • Post-transplant Lymphoproliferative Disorder
  • Recurrent Childhood Large Cell Lymphoma
  • Recurrent Childhood Lymphoblastic Lymphoma
  • Recurrent Childhood Small Noncleaved Cell Lymphoma
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
Intervention  ICMJE
  • Biological: rituximab
    Given IV
    Other Names:
    • IDEC-C2B8
    • IDEC-C2B8 monoclonal antibody
    • Mabthera
    • MOAB IDEC-C2B8
    • Rituxan
  • Radiation: indium In 111 ibritumomab tiuxetan
    Given IV
    Other Name: IDEC-In2B8
  • Radiation: yttrium Y 90 ibritumomab tiuxetan
    Given IV
    Other Names:
    • 90Y ibritumomab tiuxetan
    • IDEC Y2B8
    • Y90 Zevalin
    • Y90-labeled ibritumomab tiuxetan
  • Procedure: peripheral blood stem cell transplantation
    Undergo PBSC transplantation
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Biological: filgrastim
    Given subcutaneously
    Other Names:
    • G-CSF
    • Neupogen
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE
  • Experimental: Group A (no planned PBSC support)

    Patients receive rituximab IV over 4-6 hours followed by 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.

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

    Interventions:
    • Biological: rituximab
    • Radiation: indium In 111 ibritumomab tiuxetan
    • Radiation: yttrium Y 90 ibritumomab tiuxetan
    • Procedure: peripheral blood stem cell transplantation
    • Other: laboratory biomarker analysis
  • Experimental: 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 G-CSF subcutaneously beginning on day 22 and continuing until blood counts recover or day 35.
    Interventions:
    • Biological: rituximab
    • Radiation: indium In 111 ibritumomab tiuxetan
    • Radiation: yttrium Y 90 ibritumomab tiuxetan
    • Procedure: peripheral blood stem cell transplantation
    • Biological: filgrastim
    • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 16, 2013)
36
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date March 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • Performance status - Lansky 50-100% (age 10 and under)
  • Performance status - Karnofsky 50-100% (age 11 to 21)
  • At least 2 months
  • 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)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 5 times ULN
  • Albumin ≥ 2 g/dL
  • Creatinine normal
  • Creatinine clearance or glomerular filtration rate ≥ 70 mL/min
  • Shortening fraction ≥ 27% by echocardiogram
  • Ejection fraction ≥ 50% by MUGA
  • 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)
  • 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
  • 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)
  • See Disease Characteristics
  • At least 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea) and recovered
  • See Disease Characteristics
  • Recovered from prior radiotherapy
  • No concurrent medications that would interact with the study drug
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT00036855
Other Study ID Numbers  ICMJE NCI-2012-01871
ADVL0013
U01CA097452 ( U.S. NIH Grant/Contract )
CDR0000069331 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mitchell Cairo Children's Oncology Group
PRS Account National Cancer Institute (NCI)
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP