Phase I/II Study of hLL1-DOX in Relapsed NHL and CLL

Gilead Sciences

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Non-Hodgkin's Lymphoma

Chronic Lymphocytic Leukemia

Treatments

Drug: hLL1-DOX (IMMU-115)

Study type

Interventional

Funder types

Industry

Identifiers

NCT01585688

IM-T-hLL1-DOX-02

Details and patient eligibility

About

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.

Full 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.

Enrollment

13 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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