Safety Study of NHL With 90Y-hLL2 IgG

Study Overview
=================
Brief Summary
-----------------
This will be an open label, multiple center, non-randomized, dose-escalation Phase I/II trial, designed to evaluate the safety and effectiveness of a repeated, outpatient regimen utilizing IMMU-hLL2 intact monoclonal antibody IgG labeled with different doses of 90Y for the treatment of patients B-cell lymphoma (NHL).

Detailed Description
-----------------
90Y-labeled hLL2 will be administered according to a schedule based upon whether or not a patient had prior high-dose chemotherapy with a marrow or stem cell transplant. Patients with both indolent and aggressive types of NHL will be enrolled at each dose level without segregation. However, at the conclusion of the trial, with the maximum tolerated dose (MTD) defined, a minimum number of 6 patients with indolent NHL, 6 patients with aggressive NHL, and 6 patients with >25% bone marrow involvement will be studied at that dose level.

Official Title
-----------------
Phase I/II Radioimmunotherapy of Non-Hodgkin's Lymphoma With Radiolabeled Humanized IMMU-LL2: Treatment With 90Y-hLL2 IgG

Conditions
-----------------
NHL, B-cell NHL, Non-Hodgkins Lymphoma

Intervention / Treatment
-----------------
* Biological: 90Y-hLL2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients must have a histologic or cytological diagnosis of B-cell lymphoma, and have failed at least one regimen of standard chemotherapy. All histologic grades of non-Hodgkin's lymphoma (NHL) will be eligible for these studies. Patients must be > 18 years of age Measurable disease by CT, with at least one lesion > 1.5 cm in one or both dimensions less than 25% bone marrow involvement as determined by bone marrow biopsy Patient must have greater than 15% cellularity of the bone marrow. Patients must be at least 4 weeks beyond any major surgery. Patients must be at least 4 weeks beyond any radiation therapy to the index lesion and must have recovered from radiation induced toxicity. Patients must be at least 4 weeks beyond prior chemotherapy and/or immunotherapy, or 2-weeks after corticosteroids, and their blood counts must be within the eligibility criteria. Corticosteroids may, however, be given concomitantly if used to treat adrenal insufficiency Patients must have a performance status of 70 or greater on the Karnofsky scale equivalent to ECOG 0-1 (See Appendix A) and a minimal life expectancy of 6 months. Patients must be able to give cognizant informed consent. Exclusion Criteria: Patients with a significant concurrent medical complication including severe anorexia, nausea or vomiting that in the judgement of the Investigator could affect the patient's ability to tolerate or complete this study. Patients with metastasis to the brain. Patients with extensive irradiation to more than 25% of their red marrow will be excluded, except those who had total body irradiation in the context of bone marrow or stem cell transplantation regimen with subsequent engraftment of a functional marrow (i.e., resulting in normal peripheral blood counts). Subjects who have received external radiation to specific organs or areas at the maximum tolerated level are also excluded. Women who test positive for pregnancy. Patients with splenomegaly. Patients with > 4 treatment regimens prior to this protocol, including chemotherapy, radiotherapy and/or other immunotherapy. Patients with prior radioimmunotherapy treatments (unless for retreatment under this protocol). Patients receiving rituximab within 3 months, unless progressing after treatment. Patients with <50% LVEF by required MUGA or 2-D ECHO. Patients with <60% of predicted value by required pulmonary function tests. Patients who have active Hepatitis B or C or are known HIV positive. Patients with another primary malignancy (except basal/squamous cell carcinoma of the skin or carcinoma in-situ of the cervix. Patients with other serious medical, surgical, or psychiatric history, unless currently stable and well controlled, without significant increase in treatment medications for at least 30 days preceding study entry.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: multi<br>escalating in increments of 2.5 mCi/m2 | Biological: 90Y-hLL2<br>* weekly dosing for either 2 or 3 weeks<br>* Other names: hLL2;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety will be evaluated from physical examinations, hematology and chemistry testing and toxicity evaluation |  | First 12 weeks, total 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine maximum tolerated dose (MTD) |  | first 12 weeks | 
| Evaluate the immunogenicity and safety of repeated infusions of 90Y-hLL2 in NHL patients. |  | 6 weeks, 12 weeks, every 3 months if HAHA elevated | 
| Determine the therapeutic effects, in terms of objective response rate and duration, of the therapeutic agent in NHL patients. |  | 6 wks, 12 wks, every 3 mos for 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NHL, B-cell NHL, Non-Hodgkins lymphoma