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

NCT01585688 | Terminated Phase 1

• 1 other identifier: IM-T-hLL1-DOX-02
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 6

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.

Conditions

Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia

Keywords

NHL; CLL

Outcome Measures

Primary Outcomes (2)

• Evaluate the safety and tolerability of hLL1-DOX

  NCI CTCAE version 4.0 is used to grade all adverse events

  These assessments will be done routinely during treatment & changes at 4, 8 & 12 weeks after treatment

• All patients who were treated and meet the efficacy criteria for response assessment will be included in the analysis of efficacy

  For the primary efficacy evaluations, the proportion of responders (defined as patients with a best response of PR or CR) will be tabulated for each dose level. In addition, the progression-free survival (PFS, as measured from start of treatment to disease progression, death or last follow-up) will be summarized using Kaplan-Meier survival analysis methods. Similarly, for responders at each dose level, the duration of response (DR, as measured from time of first response to relapse or last follow-up) will also be summarized using Kaplan- Meier survival analysis methods, if appropriate.

  During treatment and the changes at 4, 8 and 12 weeks after treatment and then every 3 months for up to 2 years

Study Arms (1)

hLL1-DOX

EXPERIMENTAL

Drug: hLL1-DOX (IMMU-115)

Interventions

hLL1-DOX (IMMU-115) 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.

Also known as: IMMU-115

hLL1-DOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (6)

Helen F. Graham Cancer Center

Newark, Delaware, 19713, United States

Location

MD Anderson Cancer Center Orlando

Orlando, Florida, 32806, United States

Location

IU Health Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

UMass Memorial Cancer Center of Excellence

Worcester, Massachusetts, 01605, United States

Location

John Theurer Cancer Center Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

U.T. MD Anderson Cancer Center Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

milatuzumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Pius P Maliakal, PhD

  Gilead Sciences

  STUDY DIRECTOR

• Francois Wilhelm, MD,PhD

  Gilead Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2012
• First Posted: April 26, 2012
• Study Start: August 1, 2012
• Primary Completion: November 1, 2016
• Study Completion: October 1, 2017
• Last Updated: October 8, 2021

Record last verified: 2020-02

Locations

US (6)