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

NCT ID: NCT01585688

Last Updated: 2021-10-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2017-10-31

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.

Conditions

Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

hLL1-DOX

Group Type: EXPERIMENTAL

hLL1-DOX (IMMU-115)

Intervention Type: DRUG

hLL1-DOX is administered intravenously at one of 4 dose levels on days 1, 4, 8 and 11 of 21-day treatment cycles, with up to 8 cycles administered.

Interventions

hLL1-DOX (IMMU-115)

hLL1-DOX is administered intravenously at one of 4 dose levels on days 1, 4, 8 and 11 of 21-day treatment cycles, with up to 8 cycles administered.

Intervention Type: DRUG

Other Intervention Names

IMMU-115

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pius P Maliakal, PhD

Role: STUDY_DIRECTOR

Gilead Sciences

Francois Wilhelm, MD,PhD

Role: STUDY_CHAIR

Gilead Sciences

Locations

Helen F. Graham Cancer Center

Newark, Delaware, United States

MD Anderson Cancer Center Orlando

Orlando, Florida, United States

IU Health Goshen Center for Cancer Care

Goshen, Indiana, United States

UMass Memorial Cancer Center of Excellence

Worcester, Massachusetts, United States

John Theurer Cancer Center Hackensack University Medical Center

Hackensack, New Jersey, United States

U.T. MD Anderson Cancer Center Houston

Houston, Texas, United States

Countries

United States

Other Identifiers

IM-T-hLL1-DOX-02

Identifier Type: -

Identifier Source: org_study_id