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90Y-Ibritumomab Tiuxetan and Autologous Hematopoietic Cell Infusion Followed by High Dose Chemotherapy and Autologous Transplantation for Relapsed or Resistant Non-Hodgkin's Lymphoma

Phase 1
18 Years
70 Years
Not Enrolling
Lymphoma, Non-Hodgkin, Blood and Marrow Transplant (BMT)

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Trial Information

90Y-Ibritumomab Tiuxetan and Autologous Hematopoietic Cell Infusion Followed by High Dose Chemotherapy and Autologous Transplantation for Relapsed or Resistant Non-Hodgkin's Lymphoma

This is a single center phase I dose escalation trial of a single course of IDEC-Y2B8
(90Y-ibritumomab tiuxetan, Zevalin) with autologous peripheral blood progenitor cell
infusion followed by high dose chemotherapy and AHCT for patients with relapsed or
refractory B-cell NHL. In step one, an imaging dose of IDEC-In2B8 (111In- ibritumomab
tiuxetan, Zevalin) will be followed one week later by IDEC-Y2B; both will be preceded by an
infusion of 250 mg/m2 rituximab. Imaging will be done immediately (within 1 hr), at 4 - 6
hours and at 1, 3, and 6 days after 90Y-ibritumomab tiuxetan.

Inclusion Criteria:

Inclusion Criteria -- Step 1

4.1 Histologically proven, recurrent or refractory, CD20+ B-cell NHL reviewed at SUMC.

4.11 The definition of recurrent disease is: previous partial response (PR) or complete
response (CR) to treatment followed by disease progression.

4.12 The definition of refractory disease is: failure to achieve a PR or CR with or
progression during primary induction therapy or subsequent salvage therapy. Patients who
respond to treatment but progress within 60 days will also be considered refractory.

4.13 CD20 expression may be determined by immunohistochemistry or flow cytometry. Whenever
possible, confirmation of CD20+ status should be made on current, active disease.

4.14 The definition of NHL will be made by SUMC pathologists using the World Health
Organization Classification of Hematopoietic and Lymphoid Tissues (Appendix A).

4.15 The diagnosis should be made by excisional biopsy whenever possible. Biopsy of
refractory or recurrent disease is preferred but fine needle aspirate with supportive
morphology and immunohistochemistry is acceptable. Paraffin tissue for tissue array
studies will be sought for every patient.

4.2 Age 18-70 years

4.21 Age will be based on actual date of birth.

4.22 Pediatric patients are not eligible for this study because they are transplanted in a
separate dedicated unit with their own protocols.

4.3 ECOG performance status 0-2 (Appendix B)

4.4 Computerized tomography scans of the chest, abdomen and pelvis within 4 weeks of
registration. Assessment of response to last chemotherapy prior to registration is

4.41 Response will be assessed according to the international consensus criteria (Cheson
et al. J Clin Oncol 17:1244, 1999)

4.42 Standard definitions of the chest, abdomen and pelvis will be used for radiographic

4.5 Gallium scan or PET scan determination of disease within 4 weeks of registration is
highly recommended.

4.51 Gallium or PET scans will be whole body scans

4.6 Bone marrow biopsy and cytogenetic analysis within 8 weeks of registration. Patients
must have no or <25% involvement of the intratrabecular bone marrow cellularity by NHL.

4.7 Adequate (> 4 x 10^6/kg CD34+) peripheral blood progenitor cells collected by

4.8 Women of child-bearing potential and sexually active males are strongly advised to use
an accepted and effective method of birth control.

4.9 No chemotherapy other than corticosteroids should be administered within 4 weeks of
the initiation of protocol therapy.

4.10 Pretreatment absolute neutrophil count > 1000/mm^3 and platelet count > 150,000/

4.11 Patients must have a pretreatment serum bilirubin < 2 x the institutional ULN,
transaminases < 2 x the institutional ULN, a serum creatinine < 2 x the institutional ULN
and measured or estimated creatinine clearance > 60 cc/min by the following formula (all
tests must be performed within 28 days prior to registration):

Estimated Creatinine Clearance = (140 age)X WT(kg) X 0.85 if female X creatinine (mg/dl)

4.12 Patients must have an EKG within 42 days prior to registration that shows no
significant abnormalities that are suggestive of active cardiac disease.

4.13 Patients must have a radionuclide ejection fraction >45% within 42 days of

4.14 Patients must have a corrected diffusion capacity 70% or greater.

4.15 Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal guidelines.

Inclusion Criteria -- Step 2

4.30 Absolute neutrophil count recovery to > 1000/mm^3 and platelet recovery count to >
100,000/ mm^3.

4.31 Corrected diffusing capacity > 60%.

4.32 Resting ejection fraction of > 45%.

4.33 Serum bilirubin < 2, SGOT (AST) < 2 x ULN, SGPT (ALT) < 2 x ULN. Creatinine < 2 x the
ULN and measured or estimated creatinine clearance > 60 cc/min.

Exclusion Criteria:Exclusion Criteria - Step 1

4.16 Patients with known allergy to etoposide or a history of Grade 3 hemorrhagic cystitis
with cyclophosphamide are not eligible.

4.17 No prior malignancy is allowed except adequately treated basal cell or squamous cell
skin cancer, in situ cervical cancer or other cancer for which the patients has been
disease-free for five years.

4.18 Patients known to be human immunodeficiency virus (HIV)-positive are ineligible
because the concern for opportunistic infection and hematologic reserve are considered to
be significantly greater in this population. The antibody test for HIV must be performed
within 42 days of registration.

4.19 Patients requiring therapy for coronary artery disease, cardiomyopathy, dysrhythmia,
or congestive heart failure are not eligible.

4.20 Pregnant or breast-feeding women are ineligible due to the known birth defects
associated with the treatments used in this study.

4.21 Patients with prior radiotherapy to >25% of the active marrow are excluded.

4.22 Patients treated previously with radioimmunotherapy are excluded.

4.23 Patients with pleural effusion or ascites are excluded.

4.24 Patients may have received prior rituximab but not within the past 4 weeks.

4.25 Patients with prior autologous transplantation are ineligible.

4.26 Patients with CNS disease are ineligible.

Exclusion Criteria - Step 2

4.33 Drop in diffusing capacity of >25% from study entry.

4.34 Drop in resting ejection fraction > 20%.

4.35 Failure to recover peripheral blood counts (ANC > 1000/mm^3 and platelet recovery
count to > 100,000/mm^3 within 4 weeks after radioimmunotherapy.

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete Response

Outcome Time Frame:


Safety Issue:


Principal Investigator

Sandra Jeane Horning

Investigator Role:

Principal Investigator

Investigator Affiliation:

Stanford University


United States: Institutional Review Board

Study ID:




Start Date:

May 2004

Completion Date:

July 2007

Related Keywords:

  • Lymphoma, Non-Hodgkin
  • Blood and Marrow Transplant (BMT)
  • Lymphoma
  • Lymphoma, Non-Hodgkin



Stanford University School of Medicine Stanford, California  94305-5317