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

Alternate Title

Radiolabeled Monoclonal Antibody, Combination Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With Recurrent or Refractory B-Cell Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over Other CMMI-C-037C-97 NCI-V99-1569, NCT00004086

Objectives

I. Determine the maximum tolerated dose and dose limiting toxicity of yttrium 
Y 90 humanized anti-CD22 LL2 (Y90 MOAB hLL2) in combination with salvage 
chemotherapy and autologous peripheral blood stem cell rescue in patients with 
recurrent or refractory B-cell malignancies.

II. Study the effect of chemotherapy on the uptake of Y90 MOAB hLL2 into tumor 
 sites and normal organs by pretherapy imaging using indium In 111 humanized 
LL2 and intratherapy imaging.

III. Determine the extent and duration of tumor response in patients receiving 
this regimen.

Entry Criteria

Disease Characteristics:

Histologically or cytologically confirmed recurrent or refractory B-cell
malignancy that has failed at least one standard therapy
 Stage II to IV non-Hodgkin's lymphoma
 B-cell chronic lymphocytic leukemia, hairy cell leukemia, or Waldenstrom's
  macroglobulinemia allowed if:
   Autologous bone marrow or peripheral blood stem cells (PBSC) with no
    greater than 5% tumor involvement available
   Estimated radiation dose to marrow no greater than 3,000 cGy (bone marrow 
    involvement of greater than 25% is allowed provided stem cell              
    contamination and predicted marrow radiation doses are below the above     
    cited cut off values)
  
At least 1 confirmed site of tumor targeted by pretherapy indium In 111
humanized LL2

Autologous peripheral blood stem cells (PBSC) or bone marrow available

No active brain metastases 

Prior/Concurrent Therapy:

Biologic therapy:
 Prior low dose radioimmunotherapy allowed 

Chemotherapy:
 No prior high dose chemotherapy with PBSC rescue
 At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:
 At least 2 weeks since prior corticosteroids and recovered

Radiotherapy:
 Prior low dose radioimmunotherapy allowed 
 Prior radiotherapy to less than 35% of red marrow allowed
 At least 4 weeks since prior radiotherapy to index lesion

Surgery:
 At least 4 weeks since major surgery

Patient Characteristics:

Age:
 18 and over

Performance status:
 ECOG 0-2
 Karnofsky 70-100%

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 less than 2 mg/dL

Renal:
 Creatinine less than 1.5 times upper limit of normal 

Cardiovascular:
 Cardiac ejection fraction greater than 50%

Pulmonary:
 DLCO greater than 60% predicted
 Forced vital capacity greater than 60% predicted

Other:
 No severe anorexia, nausea, or vomiting
 HIV negative
 No prisoners
 No concurrent significant medical complication that would preclude study
  compliance
 Not pregnant
 Negative pregnancy test
 Fertile patients must use effective contraception during and for 3 months
  after study

Expected Enrollment

Approximately 15-24 patients will be accrued for this study within 2-2.5 years.

Outline

This is a dose escalation study of yttrium Y 90 humanized anti-CD22 monoclonal 
antibody LL2 (Y90 MOAB hLL2).  

Patients receive filgrastim (G-CSF) subcutaneously daily for 5 days and 
undergo harvest of peripheral blood stem cells (PBSC) on 2 or more consecutive 
days. If an adequate number of CD34+ cells are not harvested, autologous bone 
marrow may be used. Chemotherapy-induced mobilization with filgrastim allowed.

Patients undergo pretherapy imaging with indium In 111 humanized LL2 (In111 
hLL2) for up to 40 minutes on day -7. Patients receive Y90 MOAB hLL2 for up to 
40 minutes on day 0 plus In111 hLL2, followed by Y90 MOAB hLL2 alone on day 3. 
Patients receive ifosfamide IV over 1 hour, cisplatin IV over 2 hours, and 
cytarabine IV over 2 hours on days 1 and 4. Oral etoposide is given daily on 
days 1-7. PBSC or bone marrow is reinfused on days 9-14, depending on MOAB 
clearance. 

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 3 or 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.

Trial Contact Information

Trial Lead Organizations

Garden State Cancer Center

Jack Burton, MD, Protocol chair		Ph: 973-844-7024 Email: jburton@gscancer.org

Registry Information
Official Title		A Phase I Trial of a Combined Regimen of Chemotherapy and 90Y-Labeled, Humanized LL2 (Anti-CD22) Antibody with Peripheral Stem Cell Rescue for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma
Trial Start Date		1997-06-24
Registered in ClinicalTrials.gov		NCT00004086
Date Submitted to PDQ		1999-09-02
Information Last Verified		2001-12-01