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	Treatment or Intervention	Phase
AIDS-Related Lymphoma childhood large cell lymphoma childhood lymphoblastic lymphoma childhood small noncleaved cell lymphoma post-transplant lymphoproliferative disorder recurrent and refractory childhood Hodgkin's lymphoma	Drug: filgrastim  Drug: indium In 111 ibritumomab tiuxetan  Drug: rituximab  Drug: yttrium Y 90 ibritumomab tiuxetan  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: isotope therapy  Procedure: monoclonal antibody therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: radioimmunotherapy	Phase I

Further Study Details: 

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.

• 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.

• 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.

Ages Eligible for Study:  up to  21 Years,  Genders Eligible for Study:  Both

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

California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States; Recruiting
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Lucile Packard Children's Hospital at Stanford University Medical Center, Palo Alto,  California,  94304,  United States; Recruiting
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2916,  United States; Recruiting
Georgia
      MBCCOP-Medical College of Georgia Cancer Center, Augusta,  Georgia,  30912-4000,  United States; Recruiting
Indiana
      Riley Children Cancer Center at Riley Hospital for Children, Indianapolis,  Indiana,  46202-5225,  United States; Recruiting
Louisiana
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
Maryland
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      SUNY Upstate Medical University Hospital, Syracuse,  New York,  13210,  United States; Recruiting
Ohio
      Cincinnati Children's Hospital Medical Center, Cincinnati,  Ohio,  45229-2899,  United States; Recruiting
Oregon
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States; Recruiting
      Doernbecher Children's Hospital at Oregon Health & Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104-4318,  United States; Recruiting
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
Tennessee
      St. Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States; Recruiting
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States; Recruiting
      MBCCOP - South Texas Pediatrics, San Antonio,  Texas,  78229-3900,  United States; Recruiting
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-9063,  United States; Recruiting
      Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital, Houston,  Texas,  77030-2399,  United States; Recruiting
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States; Recruiting
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States; Recruiting
Canada, Ontario
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada; Recruiting
Canada, Quebec
      Hopital Sainte Justine, Montreal,  Quebec,  H3T 1C5,  Canada; Recruiting

Study chairs or principal investigators

Mitchell S. Cairo, MD,  Study Chair,  Herbert Irving Comprehensive Cancer Center   

Study ID Numbers:  CDR0000069331; COG-ADVL0013; NCT00036855
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  May 13, 2002
ClinicalTrials.gov Identifier:  NCT00036855
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08