Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	Under 22	NCI	COG-ADVL0013 NCT00036855, ADVL0013

Objectives

1. 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)
2. 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)
3. Determine the DLT of rituximab and IDEC-Y2B8 in these patients.
4. Determine the dosimetry of indium In 111 ibritumomab tiuxetan preceded by rituximab in these patients.
5. Determine, preliminarily, the antitumor activity of rituximab and IDEC-Y2B8 in these patients.
6. Assess the immune cell depletion (B-cell and T-cell) and recovery in patients treated with this regimen.
7. Determine the human anti-mouse antibody response in patients treated with this regimen.

Entry 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 10⁶ 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

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

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/mm³
• Platelet count ≥ 100,000/mm³ 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 (SpO₂) > 94% by pulse oximetry (if there is a clinical indication for SpO₂ 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

Expected Enrollment

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

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.

Cooney-Qualter E, Krailo M, Angiolillo A, et al.: A phase I study of 90yttrium-ibritumomab-tiuxetan in children and adolescents with relapsed/refractory CD20-positive non-Hodgkin's lymphoma: a Children's Oncology Group study. Clin Cancer Res 13 (18 Pt 2): 5652s-5660s, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Mitchell Cairo, MD, Protocol chair		Ph: 212-305-8316 Email: mc1310@columbia.edu

Registry Information
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
Trial Start Date		2002-06-03
Registered in ClinicalTrials.gov		NCT00036855
Date Submitted to PDQ		2002-03-11
Information Last Verified		2005-06-07
NCI Grant/Contract Number		CA57746

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