Phase I/II Study of Different Doses and Dose Schedules of Milatuzumab (hLL1) in CLL

Study Overview
=================
Brief Summary
-----------------
This study will test different doses of anti-CD74 antibody in patients with NHL and/or CLL.

Detailed Description
-----------------
Milatuzumab (hLL1, IMMU-115), a humanized anti-CD74 monoclonal antibody. Dose escalation will utilize 4 planned dose regimens with 4.0 or 8.0 mg/kg doses administered intravenously either twice weekly (days 1 and 4) or thrice weekly (days 1, 3 and 5) for 4 consecutive weeks. The four planned dose regimens will be labeled as dose level 1 to 4 corresponding to increasing levels of the total dose of milatuzumab.

Official Title
-----------------
A Phase I/II Study of Immunotherapy With Milatuzumab (hLL1) in Patients With Chronic Lymphocytic Leukemia (CLL)

Conditions
-----------------
Chronic Lymphocytic Lymphoma

Intervention / Treatment
-----------------
* Biological: milatuzumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed diagnosis of recurrent chronic lymphocytic leukemia (by NCI criteria) Received at least one prior treatment with standard therapy (previous antibody therapy is acceptable) Measurable disease (WBC > 5,000 for CLL) See protocol for full list Exclusion Criteria: Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test Pregnancy testing is not required for post-menopausal or surgically sterilized women Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study until at least 12 weeks after the last milatuzumab infusion Prior therapy with other human or humanized monoclonal antibodies, unless HAHA tested and negative; Bulky disease by CT, defined as any single mass >10 cm in its greatest diameter Known HIV positive or active hepatitis B or C, or presence of hepatitis B surface antigens or presence of hepatitis C antibody Known autoimmune disease or presence of autoimmune phenomena At least 7 days beyond any infection requiring antibiotic use. Systemic corticosteroids within 2 weeks, except low dose regimens (prednisone, <20 mg/day, or equivalent) which may continue if unchanged. Substance abuse or other concurrent medical or psychiatric conditions that, in the Investigator's opinion, could confound study interpretation or affect the patient's ability to tolerate or complete the study.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: milatuzumab<br>different doses of hLL1 | Biological: milatuzumab<br>* two or three times a week dosing of hLL1 for a total of 4 weeks<br>* Other names: hLL1;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the anti-CD74 antibody will be evaluated based upon physical examinations, hematology and chemistry laboratory evaluations and toxicity events |  | over first 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy (to see if the study drug works) in patients with NHL and CLL |  | over the first 12 weeks, then over up to 2 years | 
| Pharmacokinetics (how the drug is processed by the body) |  | over the first 12 weeks | 
| Pharmacodynamics (how the study drug is absorbed by the body)' |  | over the first 12 weeks, then over 2 years | 
| Immunogenicity |  | over at least first 12 weeks | 
| optimal dose |  | first 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CLL