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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00720135
First received: July 19, 2008
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
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
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
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of De-Immunized DI-Leu16-IL2 Immunocytokine in Patients With B-Cell Non-Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Maximum tolerated dose of DI-Leu16-IL2 [ Time Frame: 6 weeks post cycle 1 of treatment ] [ Designated as safety issue: Yes ]
  • Optimal biologic dose of DI-Leu16-IL2 [ Time Frame: 6 weeks after final cycle of treatment ] [ Designated as safety issue: Yes ]
  • Toxicities associated with the DI-Leu16-IL2 regimen [ Time Frame: 6 weeks after final cycle of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunogenicity as a result of DI-Leu16-IL2 administration [ Time Frame: Within 2 weeks following a 4 week treatment period ] [ Designated as safety issue: No ]
  • Pharmacokinetics of DI-Leu16-IL2 administration [ Time Frame: 6 weeks after final cycle of treatment ] [ Designated as safety issue: No ]
  • Clinical responses and survival [ Time Frame: Within two weeks following completion of treatment ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: January 2008
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720135

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Ryotaro Nakamura Beckman Research Institute
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00720135     History of Changes
Other Study ID Numbers: 03131, NCI-2010-01228, CDR0000598679, P50CA107399
Study First Received: July 19, 2008
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma
Lymphoma, B-Cell, Marginal Zone
Lymphoma, B-Cell
Waldenstrom Macroglobulinemia
Lymphoma, Large-Cell, Anaplastic
Lymphomatoid Granulomatosis
Lymphoma, Extranodal NK-T-Cell
Intraocular Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoma, T-Cell
Precancerous Conditions
Eye Neoplasms
Neoplasms by Site
Rituximab
Antibodies

ClinicalTrials.gov processed this record on September 15, 2014