Clinical trial NCT00868478: The Humanized Monoclonal Antibody Milatuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)
Official title: Phase I-II Trial of the Anti CD74 Monoclonal Antibody-Milatuzumab as a Single Agent in Refractory Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: humanized monoclonal antibody
Lead sponsor: Kaplan Medical Center
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2009-03-25
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Milatuzumab is effective in patients with refractory chronic lymphocytic leukemia, and also to find out in which range of doses is a response seen.

Detailed description: The aim of this study is to determine whether the anti-CD74 monoclonal antibody Milatuzumab provides benefit to subjects with CLL in advanced stage or progressive disease. The primary objectives of this study are to assess response rate to the agent, as well as the safety in CLL, using different doses: Overall response (OR), complete response (CR) and partial response (PR) will be determinate according to the NCI criteria.

The secondary objectives are to determine: duration of response, time to progression, overall survival, and the range of doses in which efficacy is seen and MTD not reached.

This study will be done in parallel with other phase I-II studies conducted by Immunomedics.

The study design will take into account that the high levels of circulating CD74expressing cells in CLL may affect both the acute (although probably not long term) toxicity and the efficacy of the study medication. This could translate to a different MTD and a different cumulative dose of Milatuzumab, needed to achieve response.(either a higher dose or longer treatment period.).

The study will be divided into two treatment phases. In the first phase we aim to address whether the dose of 120 mg/m2 is effective in CLL, and also if it is safe. In the second phase we will assess the safety and possible efficacy of higher doses, in those patients that did not achieve a significant response in the first phase. This will be done by gradual dose escalations, not to exceed 600 mg, or the MTD reached in other studies.

In addition, the study will aim at gaining further understanding of the effect of Milatuzumab on the biological in-vitro function of CLL cells.

Eligibility criteria: Inclusion Criteria:

* B-CLL confirmed according to NCI criteria
* CLL relapsed or refractory to prior antineoplastic therapy
* Signs of progressive disease; at least one:

  * B symptoms
  * lymphocyte doubling time of \< 6 months
  * symptomatic lymphadenopathy or splenomegaly
  * cytopenias due to bone marrow failure)
* Age \> 18 years, and less then 80
* Serum ALAT, ASAT, bilirubin, creatinine \< 2x upper limit of normal
* Life expectancy \> 6 months
* Patient's written informed consent

Exclusion Criteria:

* Active bacterial or viral infection
* Hypersensitivity to humanized monoclonal antibodies
* Concurrent antineoplastic treatment for CLL or other malignant disease
* Absolute neutrophil count \< 1.5 K/

Primary outcomes:
measure: Response to treatment
timeFrame: 12 weeks, 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Rehovot
country: Israel
facility: Kaplan Medical Center
Study officials:
affiliation: Kaplan Medical Center
name: Michal Haran, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Binsky I, Haran M, Starlets D, Gore Y, Lantner F, Harpaz N, Leng L, Goldenberg DM, Shvidel L, Berrebi A, Bucala R, Shachar I. IL-8 secreted in a macrophage migration-inhibitory factor- and CD74-dependent manner regulates B cell chronic lymphocytic leukemia survival. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13408-13. doi: 10.1073/pnas.0701553104. Epub 2007 Aug 8.