Ipilimumab and Rituximab In Treating Patients With Relapsed or Refractory B-Cell Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01729806
First received: November 14, 2012
Last updated: June 30, 2014
Last verified: March 2014
  Purpose

This partially randomized phase I trial studies the side effects and best dose of ipilimumab when given together with rituximab in treating patients with relapsed or refractory B-cell lymphoma. Monoclonal antibodies, such as ipilimumab and 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.


Condition Intervention Phase
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Chronic Lymphocytic Leukemia
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 Acute Lymphoblastic Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Testicular Lymphoma
Waldenström Macroglobulinemia
Biological: ipilimumab
Biological: rituximab
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Ipilimumab in Combination With Rituximab in Patients With Relapsed/Refractory CD20+ B-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of toxicities according to the Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
    Tables will be created to summarize the toxicities and side effects by dose, course, organ and severity.


Secondary Outcome Measures:
  • Immune response as measured by the frequency of activated T-cells, absolute lymphocyte count, antibody dependent cell-mediated cytotoxicity, and kinetics and magnitude of B-cell depletion [ Time Frame: Up to 14 weeks ] [ Designated as safety issue: No ]
    Regression methods (adapted for repeated measures) will be used to describe the changes over time. In addition to summarizing the changes over time within each arm, these regression models will contain contrasts to compare the two arms in terms of changes.

  • Clinical anti-tumor response (complete response and partial response as per International workshop lymphoma response criteria [Cheson 2007]) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: From when the patient started treatment to the time the patient is first recorded as having disease relapse/progression, or to the date of death if the patient dies due to causes other than disease progression, assessed up to 12 months ] [ Designated as safety issue: No ]
    Progression-free survival will be summarized using Kaplan-Meier plots.


Estimated Enrollment: 38
Study Start Date: November 2012
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (ipilimumab and rituximab)
Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 1, 4, 7, and 10. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
Biological: ipilimumab
Given IV
Other Names:
  • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
  • MDX-010
  • MDX-CTLA-4
  • monoclonal antibody CTLA-4
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm B (ipilimumab and rituximab)
Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 3, 6, 9, and 12. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
Biological: ipilimumab
Given IV
Other Names:
  • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
  • MDX-010
  • MDX-CTLA-4
  • monoclonal antibody CTLA-4
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine a recommended phase II dose for ipilimumab in combination with rituximab.

SECONDARY OBJECTIVES:

I. To obtain preliminary information on the effect of adding ipilimumab to rituximab in regard to: immune response; clinical anti-tumor response/overall remission rate (ORR) (complete remission + partial remission); progression free survival (PFS).

OUTLINE: This is a dose-escalation study of ipilimumab followed by a randomized study.

PART I:

INDUCTION: Patients receive ipilimumab intravenously (IV) over 90 minutes once every 3 weeks for 12 weeks and rituximab IV over 2-6 hours once weekly for 4 weeks.

MAINTENANCE: Patients receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year.

PART II: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 1, 4, 7, and 10. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 3, 6, 9, and 12. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 12 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previously treated, histologically confirmed cluster of differentiation (CD)20+ B cell lymphoma; bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies or extra nodal biopsies; fine needle aspirates are not acceptable
  • All patients must be informed of the investigative nature of the clinical trial and give written informed consent in accordance with institutional and federal guidelines
  • Able to adhere to the study visit schedule and other protocol requirements
  • Karnofsky >= 70%
  • Life expectancy expected to be greater than 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 50,000/mcL
  • Total bilirubin =< 2.0 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Serum creatinine =< 2.0 x upper limit of normal or calculated creatinine clearance >= 30 ml/min/1.73 M^2 by the modified Cockcroft and Gault Formula or creatinine clearance >= 30 mL/min obtained from a 24-hour urine collection
  • At least one measurable lesion according to International workshop lymphoma response criteria (Cheson 2007); there must be measurable lymphadenopathy to follow with serial exam and/or imaging
  • All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study
  • Patients must have evidence of progression of disease during or after last treatment
  • Submission of original biopsy for review and verification by Participating Center hematopathologist
  • Disease free of prior malignancies for >= 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients with a history of prior treatment with ipilimumab
  • Patients with a history of prior treatment with an anti-PD 1 antibody, CD137 agonist or other immune activating therapy such as anti-CD 40 antibody are excluded unless 5 half-lives of the agent (minimum of 8 weeks) have intervened since the therapy; patients who have received prior vaccine therapy are eligible
  • Patients who are receiving any other investigational agents
  • Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis, multiple sclerosis)
  • Patients with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte antigen 4 (CTLA 4) antibody
  • Patients with known brain metastases are excluded
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab
  • Patients on systemic corticosteroids (except for patients on stable doses of hormone replacement therapy such as hydrocortisone), or other immunosuppressants (e.g., infliximab, mycophenolate mofetil) are excluded
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections are excluded
  • Pregnant women are excluded from this study
  • HIV-positive patients on combination antiretroviral therapy are ineligible
  • Rituximab within six weeks
  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: NCT01729806

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Leslie L. Popplewell    626-256-4673    lpopplewell@coh.org   
Principal Investigator: Leslie L. Popplewell         
University of Southern California/Norris Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Ann Mohrbacher    323-865-3924    mohrbach@usc.edu   
Principal Investigator: Ann Mohrbacher         
City of Hope Medical Group Inc Recruiting
Pasadena, California, United States, 91105
Contact: Stephen C. Koehler    626-396-2900    Skhehler@cohmg.com   
Principal Investigator: Stephen C. Koehler         
University of California at Davis Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Joseph M. Tuscano    916-734-3771    joseph.tuscano@ucdmc.ucdavis.edu   
Principal Investigator: Joseph M. Tuscano         
United States, Pennsylvania
Penn State Milton S Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Jeffrey J. Pu    717-531-8399    jeffreypu@hmc.psu.edu   
Principal Investigator: Jeffrey J. Pu         
Sponsors and Collaborators
Investigators
Principal Investigator: Joseph Tuscano Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01729806     History of Changes
Other Study ID Numbers: NCI-2012-02213, NCI-2012-02213, CDR0000743246, PHI-69, 9197, U01CA062505, P30CA033572
Study First Received: November 14, 2012
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Hairy Cell
Burkitt Lymphoma
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Mantle-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 24, 2014