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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01729806
• Date of registration: 14/11/2012
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Ipilimumab and Rituximab in Treating Patients With Relapsed or Refractory B-cell Lymphoma
• Scientific title: A Phase I Study of Ipilimumab in Combination With Rituximab in Patients With Relapsed/Refractory CD20+ B-Cell Lymphoma
• Date of first enrolment: November 19, 2012
• Target sample size: 32
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01729806
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Joseph Tuscano
• Affiliation: City of Hope Comprehensive Cancer Center

Key inclusion & exclusion 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; 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

CD20 Positive

Refractory B-Cell Non-Hodgkin Lymphoma

Recurrent B-Cell Non-Hodgkin Lymphoma

Intervention(s)

Other: Laboratory Biomarker Analysis

Biological: Ipilimumab

Biological: Rituximab

Primary Outcome(s)

Incidence of toxicities according to the Common Terminology Criteria for Adverse Events version 4 [Time Frame: Up to 12 months]

Secondary Outcome(s)

Clinical anti-tumor response (complete response and partial response as per international workshop lymphoma response criteria [Cheson 2007]) [Time Frame: Up to 12 months]

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]

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]

Secondary ID(s)

P30CA033572

UM1CA186717

NCI-2012-02213

CDR0000743246

PHI-69

9197

U01CA062505

NCI# 9197

UM1CA186704

Source(s) of Monetary Support

Please refer to primary and secondary sponsors