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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


Phase 1
N/A
21 Years
Not Enrolling
Both
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

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD, defined as that dose at which fewer than one-third of patients experience DLT graded according to the NCI CTC v 2.0

Outcome Time Frame:

Up to day 49

Safety Issue:

Yes

Principal Investigator

Mitchell Cairo

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01871

NCT ID:

NCT00036855

Start Date:

June 2002

Completion Date:

Related Keywords:

  • 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
  • Acquired Immunodeficiency Syndrome
  • Hodgkin Disease
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoproliferative Disorders
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

Children's Oncology GroupArcadia, California  91006-3776