Ipilimumab and Rituximab in Treating Patients With Relapsed or Refractory B-cell Lymphoma

NCT ID: NCT01729806

Last Updated: 2018-04-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-19

Study Completion Date

2018-03-30

Brief Summary

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This partially randomized phase I trial studies the side effects and best dose of ipilimumab when given together with rituximab in treating patients with B-cell lymphoma that has returned or has not responded to treatment. Monoclonal antibodies, such as ipilimumab and rituximab, may interfere with the ability of cancer cells to grow and spread.

Detailed Description

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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 B: 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.

Conditions

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CD20 Positive Recurrent B-Cell Non-Hodgkin Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Rituximab

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Rituximab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Ipilimumab

Given IV

Intervention Type BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Rituximab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 MDX-010 MDX-CTLA4 Yervoy ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 RTXM83

Eligibility Criteria

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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; 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-programmed cell death (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 uncontrolled brain metastases are excluded; however, patients with stable brain disease (off corticosteroids) at least 2 weeks after completion of appropriate therapy for their brain metastases are eligible
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joseph Tuscano

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Locations

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City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

City of Hope South Pasadena

South Pasadena, California, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2012-02213

Identifier Type: REGISTRY

Identifier Source: secondary_id

PHI-69

Identifier Type: -

Identifier Source: secondary_id

CDR0000743246

Identifier Type: -

Identifier Source: secondary_id

NCI# 9197

Identifier Type: -

Identifier Source: secondary_id

9197

Identifier Type: OTHER

Identifier Source: secondary_id

9197

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062505

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UM1CA186717

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02213

Identifier Type: -

Identifier Source: org_study_id

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