Clinical trial NCT01585688: Phase I/II Study of hLL1-DOX in Relapsed NHL and CLL
Official title: A Phase I/II Study of Immunotherapy With hLL1-DOX in Patients With Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Lymphoma
Chronic Lymphocytic Leukemia
Keywords: NHL
CLL
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-04-26
Enrollment: 13
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: The primary objectives are to evaluate the safety and tolerability of hLL1-DOX, and to determine the maximum tolerated dose (MTD) regimen (in terms of a dose and its associated dosing schedule). The secondary objectives are to obtain information on efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity, and to determine the optimal dose for subsequent studies.

Detailed description: Patients receive hLL1-DOX at one of 4 dose levels administered on Days 1, 4, 8 and 11 of 21-day treatment cycles which are continued in the absence of progression or unacceptable toxicity up to a total of 8 cycles. After treatment, follow-up will be done at 4, 8 and 12 weeks post-treatment and will continue to be done every 3 months for up to 2 years.

Eligibility criteria: Inclusion Criteria:

* Male or female, age ≥ 18 years
* Able to provide signed, informed consent
* Histologically confirmed diagnosis of recurrent B-cell non-Hodgkin's lymphoma (any histology by WHO criteria) or recurrent chronic lymphocytic leukemia (by NCI criteria) (Reference Appendix C)
* Received at least one prior treatment with standard therapy (previous antibody therapy is acceptable)
* Measurable disease at least one lesion ≥ 1.5 cm for NHL and ALC \> 5,000 for CLL
* Adequate performance status (≥ 70 Karnofsky scale) with an estimated life expectancy of at least 6 months

  --Documented negative hepatitis B screen, per NCCN guidelines (hepatitis B surface antigen/antibodies, core antigen/antibodies, hepatitis B e-antigen)
* At least 12 weeks beyond stem cell transplant and 4 weeks beyond chemotherapy or immunotherapy, major surgery, other experimental treatments, or radiation therapy to the index lesions, and with all acute toxicities from prior therapy resolved to less than Grade 2 toxicity by NCI CTC version 4.0
* Laboratory parameters:

Adequate hematology without ongoing transfusional support Hemoglobin \>/= 10 g/dL Absolute neutrophil count \>/= 1.5 x 10 9/L Platelets \>/= 75 x 10 9/L Creatinine and bilirubin \</= 1.5 x IULN AST and ALT \</= 2.5 x IULN

-Adequate cardiac function (MUGA scan or 2-D ECHO with LVEF ≥ 55%, EKG with no medically relevant arrhythmia uncontrolled on medications)

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
* Prior treatment with trastuzumab
* 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
* New York Heart Classification III or IV heart disease (see Appendix G). Other severe cardiovascular or cardiopulmonary disease, including COPD
* Baseline BNP \> 2 x IULN
* Patients with uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities will be excluded
* Patients with recent (≤ 6 months) cardiac angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias will be excluded
* Known autoimmune disease or presence of autoimmune phenomena
* At least 7 days beyond any infection requiring intravenous antibiotic use (Oral antibiotics may be administered prophylactically as clinically indicated)
* 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: Evaluate the safety and tolerability of hLL1-DOX
timeFrame: These assessments will be done routinely during treatment & changes at 4, 8 & 12 weeks after treatment
measure: All patients who were treated and meet the efficacy criteria for response assessment will be included in the analysis of efficacy
timeFrame: During treatment and the changes at 4, 8 and 12 weeks after treatment and then every 3 months for up to 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Newark
country: United States
facility: Helen F. Graham Cancer Center
state: Delaware
city: Orlando
country: United States
facility: MD Anderson Cancer Center Orlando
state: Florida
city: Goshen
country: United States
facility: IU Health Goshen Center for Cancer Care
state: Indiana
city: Worcester
country: United States
facility: UMass Memorial Cancer Center of Excellence
state: Massachusetts
city: Hackensack
country: United States
facility: John Theurer Cancer Center Hackensack University Medical Center
state: New Jersey
city: Houston
country: United States
facility: U.T. MD Anderson Cancer Center Houston
state: Texas
Study officials:
affiliation: Gilead Sciences
name: Pius P Maliakal, PhD
role: STUDY_DIRECTOR
affiliation: Gilead Sciences
name: Francois Wilhelm, MD,PhD
role: STUDY_CHAIR
References: