Clinical trial NCT00603668: Phase I/II Study of Different Doses and Dose Schedules of Milatuzumab (hLL1) in CLL
Official title: A Phase I/II Study of Immunotherapy With Milatuzumab (hLL1) in Patients With Chronic Lymphocytic Leukemia (CLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Lymphoma
Keywords: CLL
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2008-01-29
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety of the anti-CD74 antibody will be evaluated based upon physical examinations, hematology and chemistry laboratory evaluations and toxicity events
timeFrame: over first 12 weeks
Secondary outcomes:
measure: Efficacy (to see if the study drug works) in patients with NHL and CLL
timeFrame: over the first 12 weeks, then over up to 2 years
measure: Pharmacokinetics (how the drug is processed by the body)
timeFrame: over the first 12 weeks
measure: Pharmacodynamics (how the study drug is absorbed by the body)'
timeFrame: over the first 12 weeks, then over 2 years
measure: Immunogenicity
timeFrame: over at least first 12 weeks
measure: optimal dose
timeFrame: first 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Washington
country: United States
facility: Georgetown University Hospital Lombardi Cancer Center
state: District of Columbia
city: Orlando
country: United States
facility: M. D. Anderson Cancer Center
state: Florida
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Gilead Sciences
name: William Wegener, MD, PhD
role: STUDY_CHAIR
References:
citation: Stein R, Mattes MJ, Cardillo TM, Hansen HJ, Chang CH, Burton J, Govindan S, Goldenberg DM. CD74: a new candidate target for the immunotherapy of B-cell neoplasms. Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5556s-5563s. doi: 10.1158/1078-0432.CCR-07-1167.
citation: Stein R, Qu Z, Cardillo TM, Chen S, Rosario A, Horak ID, Hansen HJ, Goldenberg DM. Antiproliferative activity of a humanized anti-CD74 monoclonal antibody, hLL1, on B-cell malignancies. Blood. 2004 Dec 1;104(12):3705-11. doi: 10.1182/blood-2004-03-0890. Epub 2004 Aug 5.