Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

June 3, 2015 updated by: City of Hope Medical Center

A Phase I Study of De-Immunized DI-Leu16-IL2 Immunocytokine in Patients With B-Cell Non-Hodgkin Lymphoma

RATIONALE: Biological therapies, such as fusion protein cytokine therapy, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving fusion protein cytokine therapy together with rituximab may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of fusion protein cytokine therapy when given after rituximab in treating patients with B-cell non-Hodgkin lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of DI-Leu16-IL2 (DI-Leu16-IL2 immunocytokine) following peripheral blood B cell depletion with rituximab in patients with B-cell NHL.

II. To investigate the optimal biological dose (OBD) of DI-Leu16-IL2 following peripheral blood B cell depletion with rituximab in patients with B-cell NHL, which may differ from the MTD.

III. To describe the toxicities associated with the proposed DI-Leu16-IL2 regimen.

SECONDARY OBJECTIVES:

I. To evaluate the immunogenicity as measured by the induction of DI-Leu16-IL2-specific antibodies.

II. To evaluate the pharmacokinetics of DI-Leu16-IL2. III. To document any clinical responses associated with the proposed therapy and survival endpoints of the enrolled patients.

OUTLINE: This is a dose-escalation study of DI-Leu16-IL2 immunocytokine.

Patients receive DI-Leu16-IL2 immunocytokine IV over 4 hours on 4 consecutive Wednesdays.

Patients with detectable CD20-positive B-cells pretreatment also receive rituximab IV on 4 consecutive Tuesdays.

Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 5 years.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion

  • Patients with CD20-expressing B cell NHL that is relapsed or refractory to standard therapy; CLL/SLL with peripheral blood leukemia/lymphoma cells and high-grade lymphomas (i.e., lymphoblastic lymphoma/Burkitt lymphoma) are excluded
  • Patients must have received prior Rituxan
  • Measurable disease; in the absence of lymphadenopathy, splenomegaly with defects or measurable extramedullary disease is acceptable; however, bone marrow involvement alone will not be included in the study
  • Age >=18 years and <=65 physiologic years of age
  • KPS >= 70%
  • Life expectancy >= 12 weeks
  • Serum creatinine =< 1.5 mg/dl
  • Total WBC >= 3000/ul or absolute neutrophil count (ANC) >= 1000/ul
  • Lymphocyte count >= 0.2 x 10^3/ul
  • Platelet count >= 75,000/ul
  • Hematocrit >= 25% or hemoglobin >= 9 g/100 ml
  • Alanine aminotransferase (ALT) =< 2.5 x UNL
  • Aspartate aminotransferase (AST) =< 2.5 x UNL
  • Total bilirubin (TBili) < 1.5 x UNL
  • Sodium, potassium, and phosphorus within normal limits
  • Chest x ray (CXR) within 4 weeks prior to Day 1 with no evidence of pulmonary congestion, pleural effusions, pulmonary fibrosis, or significant emphysema; if results are questionable, subjects would have additional lung function testing to exclude clinically relevant restriction or obstruction; subjects must have an FEV-1 and DLCO of at least 65% and 50% of expected, respectively
  • Electrocardiogram (12-lead ECG)
  • Echocardiogram (or MUGA) with normal left ventricular function
  • Cardiac stress test (e.g., stress thallium scan, stress echocardiography) with normal results if subject is suspected to have coronary artery disease
  • Fasting blood glucose (FBG) < 160 and hemoglobin (Hgb) A1C < 7% for subjects with diabetes mellitus (DM) or borderline DM
  • Women of procreative potential must have negative pregnancy test within the 2-week screening phase prior to Cycle 1, and all subjects of procreative potential must use adequate birth control throughout the study; subjects of procreative potential are defined as any fertile male, and any female who has experienced menarche and has not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy) or is not post-menopausal, defined as age-related amenorrhea >= 12 months
  • Provide written informed consent prior to any screening procedures

Exclusion

  • Evidence of CNS lymphoma or lymphomatous meningitis
  • Prior treatment with IL-2
  • Type I hypersensitivity or anaphylactic reactions to murine proteins or to previous infusion of rituximab
  • Pregnant or lactating female
  • An immediate need for palliative radiotherapy or systemic corticosteroid therapy
  • Known intercurrent infections (including hepatitis C virus [HCV] and HIV or other conditions), or clinical evidence of these conditions
  • Actively infected with or chronic carriers of hepatitis B virus (HBV) as demonstrated by positive hepatitis B core antibody (HbcHb) or hepatitis B surface antigen (HbsAg); (subjects who are sero-positive only, i.e., surface antibody positive [HbsAg], are permitted)
  • Other significant active infection
  • Major surgery, chemotherapy, investigational agent, or radiation within 30 days of Day 1
  • Uncontrolled hypertension (diastolic >= 100 mmHg) or hypotension (systolic =< 90 mmHg)
  • History of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other significant arrhythmias
  • On ECG: a marked baseline prolongation of QT/QTc interval (> grade 2 QTc interval > 470 milliseconds)
  • History of medically significant ascites requiring repetitive paracentesis
  • Previous diagnosis of Addison's disease
  • Previous diagnosis of autoimmune disease (exceptions: subjects with autoimmune thyroiditis or vitiligo may be enrolled)
  • Organ transplant recipient
  • History of prior therapy or a serious, uncontrolled medical disorder that in the investigator's opinion would impair participation in the study
  • Known hypersensitivity to Tween-80 or human immunoglobulin
  • Legal incapacity or limited legal capacity
  • Patients with bulky lymph nodes (>= 10cm) or marked splenomegaly (i.e., extending into pelvis or crossing the midline)
  • Positive anti-DI-Leu16-IL2 antibody assay (where positive is defined as > 10% of the radiolabeled DI-Leu16-IL2 reactive with the subject's serum)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I
Patients receive DI-Leu16-IL2 immunocytokine IV over 4 hours on 4 consecutive Wednesdays. Patients with detectable CD20-positive B-cells pretreatment also receive rituximab IV on 4 consecutive Tuesdays. Treatment repeats every 6-8 weeks for up to a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
Correlative studies
Other: flow cytometry
Correlative studies
Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • C2B8 Monoclonal Antibody
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Other: immunohistochemistry staining method
Correlative studies
Other Names:
  • immunohistochemistry
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Names:
  • ELISA
Genetic: reverse transcriptase-polymerase chain reaction
Correlative studies
Other Names:
  • RT-PCR
Biological: DI-Leu16-IL2 immunocytokine
Given IV
Other Names:
  • de-immunized anti-CD20-IL-2 immunocytokine DI-Leu16-IL-2
  • DI-Leu16-IL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose of DI-Leu16-IL2
Time Frame: 6 weeks post cycle 1 of treatment
6 weeks post cycle 1 of treatment
Optimal biologic dose of DI-Leu16-IL2
Time Frame: 6 weeks after final cycle of treatment
6 weeks after final cycle of treatment
Toxicities associated with the DI-Leu16-IL2 regimen
Time Frame: 6 weeks after final cycle of treatment
6 weeks after final cycle of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Immunogenicity as a result of DI-Leu16-IL2 administration
Time Frame: Within 2 weeks following a 4 week treatment period
Within 2 weeks following a 4 week treatment period
Pharmacokinetics of DI-Leu16-IL2 administration
Time Frame: 6 weeks after final cycle of treatment
6 weeks after final cycle of treatment
Clinical responses and survival
Time Frame: Within two weeks following completion of treatment
Within two weeks following completion of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2008

Primary Completion (ACTUAL)

July 1, 2014

Study Completion (ACTUAL)

July 1, 2014

Study Registration Dates

First Submitted

July 19, 2008

First Submitted That Met QC Criteria

July 19, 2008

First Posted (ESTIMATE)

July 22, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

June 8, 2015

Last Update Submitted That Met QC Criteria

June 3, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03131
  • P50CA107399 (U.S. NIH Grant/Contract)
  • NCI-2010-01228
  • CDR0000598679 (REGISTRY: PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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