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

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ClinicalTrials.gov Identifier: NCT00720135
Recruitment Status : Completed
First Posted : July 22, 2008
Last Update Posted : June 8, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE July 19, 2008
First Posted Date  ICMJE July 22, 2008
Last Update Posted Date June 8, 2015
Study Start Date  ICMJE January 2008
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2010)
  • Maximum tolerated dose of DI-Leu16-IL2 [ Time Frame: 6 weeks post cycle 1 of treatment ]
  • Optimal biologic dose of DI-Leu16-IL2 [ Time Frame: 6 weeks after final cycle of treatment ]
  • Toxicities associated with the DI-Leu16-IL2 regimen [ Time Frame: 6 weeks after final cycle of treatment ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 19, 2008)
  • Maximum tolerated dose
  • Optimal biologic dose
  • Toxicity
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2010)
  • Immunogenicity as a result of DI-Leu16-IL2 administration [ Time Frame: Within 2 weeks following a 4 week treatment period ]
  • Pharmacokinetics of DI-Leu16-IL2 administration [ Time Frame: 6 weeks after final cycle of treatment ]
  • Clinical responses and survival [ Time Frame: Within two weeks following completion of treatment ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2008)
  • Immunogenicity
  • Pharmacokinetics
  • Clinical response
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma
Official Title  ICMJE A Phase I Study of De-Immunized DI-Leu16-IL2 Immunocytokine in Patients With B-Cell Non-Hodgkin Lymphoma
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Anaplastic Large Cell Lymphoma
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Intraocular Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Testicular Lymphoma
  • Waldenstrom Macroglobulinemia
Intervention  ICMJE
  • Biological: DI-Leu16-IL2 immunocytokine
    Given IV
    Other Names:
    • de-immunized anti-CD20-IL-2 immunocytokine DI-Leu16-IL-2
    • DI-Leu16-IL-2
  • Biological: rituximab
    Given IV
    Other Names:
    • C2B8 Monoclonal Antibody
    • IDEC-C2B8
    • IDEC-C2B8 monoclonal antibody
    • Mabthera
    • MOAB IDEC-C2B8
    • Rituxan
  • Other: flow cytometry
    Correlative studies
  • Other: immunohistochemistry staining method
    Correlative studies
    Other Name: immunohistochemistry
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: enzyme-linked immunosorbent assay
    Correlative studies
    Other Name: ELISA
  • Genetic: reverse transcriptase-polymerase chain reaction
    Correlative studies
    Other Name: RT-PCR
Study Arms  ICMJE 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.
Interventions:
  • Biological: DI-Leu16-IL2 immunocytokine
  • Biological: rituximab
  • Other: flow cytometry
  • Other: immunohistochemistry staining method
  • Other: pharmacological study
  • Other: laboratory biomarker analysis
  • Other: enzyme-linked immunosorbent assay
  • Genetic: reverse transcriptase-polymerase chain reaction
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 14, 2014)
9
Original Enrollment  ICMJE
 (submitted: July 19, 2008)
36
Actual Study Completion Date  ICMJE July 2014
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00720135
Other Study ID Numbers  ICMJE 03131
NCI-2010-01228
CDR0000598679 ( Registry Identifier: PDQ )
P50CA107399 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party City of Hope Medical Center
Study Sponsor  ICMJE City of Hope Medical Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Ryotaro Nakamura City of Hope Medical Center
PRS Account City of Hope Medical Center
Verification Date June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP