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

Alternate Title

Monoclonal Antibody Therapy in Treating Patients With Recurrent Non-Hodgkin's Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed Not specified Pharmaceutical / Industry UNMC-289-97 IM-h-LL2-01, NCI-V97-1353

Objectives

I.  Determine the efficacy of humanized monoclonal antibody LL2 (hLL2) in 
patients with recurrent non-Hodgkin's lymphoma.

II.  Determine the safety of hLL2 in this patient population.

III.  Assess therapeutic response for protein dose dependency.

IV.  Monitor mononuclear blood cells, immunoglobulins, and hLL2 levels in 
peripheral blood during treatment.

V.  Evaluate the immunogenicity of a fractionated dose schedule of hLL2 in 
non-Hodgkin's lymphoma patients by measuring human anti-hLL2 responses.

Entry Criteria

Disease Characteristics:

Histologically confirmed recurrent or refractory B-cell non-Hodgkin's lymphoma
(NHL)
 Indolent or aggressive

Must have failed at least 1 standard NHL chemotherapy regimen

Patients with aggressive NHL who are transplant candidates must have failed
high dose chemotherapy and transplant

At least one measurable lesion at least 1.5 cm required

No single lymph node greater than 5 cm by CT scanning

No high tumor burden, especially patients with leukemic phase

Prior/Concurrent Therapy:

Biologic therapy:
 No prior human or humanized monoclonal antibodies, unless human anti-hLL2
  negative
 At least 4 weeks since prior biologic therapy, including interferon therapy

Chemotherapy:
 At least 4 weeks since prior chemotherapy, unless recovered from all
  treatment-related toxicity and have clear evidence of progressive disease

Endocrine therapy:
 At least 4 weeks since prior corticosteroids

Radiotherapy:
 At least 4 weeks since radiation therapy to the index lesion, unless
  recovered from all treatment-related toxicity and have clear evidence of
  progressive disease
 Must have recovered from any radiation-induced lymphocytopenia

Surgery:
 At least 2 weeks since any major surgery, unless recovered and have clear
  evidence of progressive disease

Other:
 No other investigational agents, unless follow-up is completed and patient is
  off study

Patient Characteristics:

Age:
 16 and over

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

Life expectancy:
 At least 4 months

Hematopoietic:
 Not specified

Hepatic:
 Bilirubin no greater than 2 mg/dL

Renal:
 Creatinine no greater than 1.5 mg/dL OR
 Creatinine clearance at least 50 mL/min

Other:
 Hepatitis B or C negative
 HIV negative
 Not human anti-hLL2 antibody positive
 No known or suspected hypersensitivity to humanized monoclonal IgG antibody
  (MAb hLL2)
 No significant concurrent medical condition
 Not pregnant or nursing
 Adequate contraception required of all fertile patients

Expected Enrollment

A total of 36 patients may be accrued into this study.

Outline

This is an open label, dose escalation study.  Patients are stratified by type 
of non-Hodgkin's lymphoma (indolent vs aggressive).

All patients receive fractionated humanized monoclonal antibody LL2 (hLL2) 
infusions twice weekly with a minimum of 2 days apart from each other.  In the 
absence of unacceptable dose toxicity, patients are accrued in cohorts of 3 
and assigned to 1 of 4 levels of increasing dosages.  If, after these 4 dose 
levels, treatment is successful, then 2 further dose escalation cohorts are 
accrued.  If after the 4 levels, dosage has reached its optimum, 2 dose 
reduction cohorts are accrued.  

Escalation stops at any dose level if there are 2 or more patients who 
experience dose-limiting toxicity (DLT).  If one person experiences DLT, an 
additional 3 patients are accrued at that same level.  If there is no 
dose-limiting toxicity in this second cohort, dose escalation continues.  If 
there is a second DLT at that level in the second cohort, treatment at that 
level stops and patients are accrued at the previous dose level.

Patients are followed every 3-4 months for the first year, then every 6 months 
until relapse.

Trial Contact Information

Trial Lead Organizations

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Julie Vose, MD, Protocol chair		Ph: 402-559-3848 Email: jmvose@unmc.edu