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Phase I/II Radioimmunotherapy of Non-Hodgkin's Lymphoma With High-Dose 90Y-Labeled Humanized LL2 Anti-CD-22 Antibody and Peripheral Blood Stem Cell Rescue

Phase 1/Phase 2
18 Years
80 Years
Not Enrolling
Leukemia, Lymphoma

Thank you

Trial Information

Phase I/II Radioimmunotherapy of Non-Hodgkin's Lymphoma With High-Dose 90Y-Labeled Humanized LL2 Anti-CD-22 Antibody and Peripheral Blood Stem Cell Rescue

OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of
radioimmunotherapy using high dose yttrium Y 90 humanized anti-CD22 monoclonal antibody LL2
(Y90 MOAB hLL2) followed by autologous peripheral blood stem cell transplantation in
patients with B cell lymphomas or Waldenstrom's macroglobulinemia. II. Determine the organ
and tumor dosimetry for comparison to clinical measurement of toxicity and antitumor
responses in these patients. III. Determine magnitude and duration of human anti-humanized
LL2 antibody (HAhLL2) or anti-DOTA response in these patients. IV. Evaluate the extent and
duration of antitumor response to this regimen in these patients.

OUTLINE: This is a dose escalation, multicenter study. Patients are stratified according to
prior treatment (high dose chemotherapy with transplantation vs low dose chemotherapy with
radioimmunotherapy (RAIT) vs low dose chemotherapy without RAIT). Patients receive
filgrastim (G-CSF) subcutaneously (SC) daily for 5 days and undergo harvest of peripheral
blood stem cells (PBSC). If an adequate number of CD34+ cells are not harvested, autologous
bone marrow may be used. Patients undergo pretherapy imaging with indium In 111 monoclonal
antibody MN-14 (In111-MN-14) IV on day -7. If at least 1 tumor site is targeted, patients
receive high dose yttrium Y 90 humanized anti-CD22 monoclonal antibody LL2 (Y90 MOAB hLL2)
IV for up to 50 minutes on day 0. PBSC or bone marrow is reinfused approximately 7-14 days
following infusion of Y90 MOAB hLL2. Patients also receive G-CSF SC daily until 3 days after
blood counts have recovered. Cohorts of 3-6 patients receive escalating doses of Y90 MOAB
hLL2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are
followed weekly for 2 months, monthly for 6 months, and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study within 2 years.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically proven B cell lymphoma of one of
the following types: Any histologic grade of non-Hodgkin's lymphoma Chronic lymphocytic
leukemia CD22 positive acute lymphocytic leukemia Waldenstrom's macroglobulinemia Must
have failed at least 1 standard therapy Autologous peripheral blood stem cells (PBSC) or
bone marrow available Bone marrow involvement allowed if: Autologous bone marrow or PBSC
with no greater than 5% tumor involvement available Radiation dose to marrow no greater
than 3,000 cGy until 6 patients have been safely treated at that dose level At least 1
confirmed site of tumor targeted by pretherapy indium In 111 monoclonal antibody MN-14
imaging No brain metastases

PATIENT CHARACTERISTICS: Age: 18 to 80 Performance status: Karnofsky 70-100% ECOG 0-2 Life
expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Granulocyte count at
least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2.0
mg/dL AST and alkaline phosphatase less than 1.5 times upper limit of normal (ULN) in the
absence of bone involvement Renal: Creatinine less than 1.5 times ULN Cardiovascular:
Ejection fraction at least 50% Pulmonary: DLCO at least 60% of predicted Forced vital
capacity at least 60% of predicted Other: No severe anorexia, nausea, or vomiting No
concurrent significant medical complications that would preclude study participation Not
pregnant Negative pregnancy test Fertile patients must use effective contraception during
and for 3 months after study HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior radioimmunotherapy AND high dose
chemotherapy Chemotherapy: No prior high dose chemotherapy AND radioimmunotherapy At least
4 weeks since other prior chemotherapy and recovered Endocrine therapy: At least 2 weeks
since prior corticosteroids and recovered Radiotherapy: No prior radioimmunotherapy AND
high dose chemotherapy At least 4 weeks since prior radiotherapy to index lesion No prior
radiotherapy to greater than 25% of any critical organ (e.g., lung, liver, kidneys) No
prior total body irradiation Surgery: At least 4 weeks since prior major surgery

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Jack D. Burton, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Garden State Cancer Center at the Center for Molecular Medicine and Immunology


United States: Food and Drug Administration

Study ID:




Start Date:

February 1998

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Waldenstrom macroglobulinemia
  • recurrent adult acute lymphoblastic leukemia
  • refractory chronic lymphocytic leukemia
  • B-cell chronic lymphocytic leukemia
  • B-cell adult acute lymphoblastic leukemia
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • Leukemia
  • Lymphoma
  • Waldenstrom Macroglobulinemia



University of Pennsylvania Cancer Center Philadelphia, Pennsylvania  19104
St. Barnabas Medical Center Livingston, New Jersey  07039
St. Joseph's Hospital and Medical Center Paterson, New Jersey  07503
Garden State Cancer Center Belleville, New Jersey  07103