Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Primary Central Nervous System Non-Hodgkin Lymphoma

Phase II Study of Radioimmunotherapy With Zevalin (Ibritumomab Tiuxetan) Therapy for Patients With Refractory or Relapsed Primary Central Nervous System Lymphoma (PCNSL)

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01973062

Enrollment

Registered

2013-10-31

Start date

2014-03-31

Completion date

2015-06-30

Last updated

2020-07-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Primary Central Nervous System Non-Hodgkin Lymphoma

Brief summary

This phase II trial studies how well yttrium Y 90 ibritumomab tiuxetan and rituximab work in treating patients with recurrent or refractory primary central nervous system non-Hodgkin lymphoma. Radiolabeled monoclonal antibodies, such as yttrium 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving yttrium Y 90 ibritumomab tiuxetan with rituximab may kill more cancer cells.

Detailed description

PRIMARY OBJECTIVES: I. Determine the radiographic response proportion in patients with refractory or recurrent primary central nervous system lymphoma (PCNSL) to ibritumomab tiuxetan (yttrium Y 90 ibritumomab tiuxetan) when given as an intravenous infusion. SECONDARY OBJECTIVES: I. Determine the progression free survival of patients treated with ibritumomab tiuxetan when given as an intravenous infusion. II. Determine the overall survival of patients treated with ibritumomab tiuxetan when given as an intravenous infusion. III. Establish the toxicity profile of ibritumomab tiuxetan in this patient population. IV. Use positron emission tomography (PET)/magnetic resonance imaging (MRI) to map the distribution of Y-90 ibritumomab tiuxetan, and calculate the Gy delivered based on the activity found within tumor. OUTLINE: Patients receive rituximab intravenously (IV) on day 1. Within 7 to 9 days, patients receive rituximab IV and yttrium Y 90 ibritumomab tiuxetan IV in the absence of disease progression or unacceptable toxicity. Distribution and dose absorbed dose will be assessed on day 11. Quality of life will be assessed at screening, at day 1, 36, 92, and at each follow-up visit. After completion of study treatment, patients are followed every 3-6 months for 2 years.

Interventions

BIOLOGICALrituximab

Given IV

RADIATIONyttrium Y 90 ibritumomab tiuxetan

Given IV

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patients with histological diagnosis of recurrent or refractory primary central nervous system (CNS) lymphoma with at least 1 measurable gadolinium enhancing lesion on brain MRI scans * Karnofsky performance status (KPS) \>= 60 * Patients could not have had more than 3 prior therapy regimens for the treatment of PCNSL * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L * Platelets \>= 100 x 10\^9/L * Hemoglobin (Hgb) \> 10 g/dL * Serum total bilirubin =\< 1.5 x upper limit of normal (ULN) * Alanine aminotransferase (ALT) =\< 3.0 x ULN * Aspartate aminotransferase (AST) =\< 3.0 x ULN * Serum creatinine =\< 1.5 x ULN * Minimum interval since completion of radiation treatment is 12 weeks * Minimum interval since last drug therapy: * 3 weeks since the completion of non-cytotoxic agents * 4 weeks since the completion of a non-nitrosourea-containing regimen * 6 weeks since the completion of a nitrosourea-containing regimen * Patients must have signed an approved informed consent and authorization permitting release of personal health information * Patients are not on corticosteroids or on stable doses (less than 6 mg daily of dexamethasone) for more than 1 week before baseline imaging * Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception * Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission; patients with other prior malignancies must be disease-free for \>= three years

Exclusion criteria

* Pregnant or breast-feeding women * Patients unwilling or unable to comply with the protocol * Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active infection, uncontrolled diabetes, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness, etc.) that could cause unacceptable safety risks or compromise compliance with the protocol * Known diagnosis of human immunodeficiency virus (HIV) infection; prior radioimmunotherapy, prior myeloablative therapy with autologous bone marrow transplantation or peripheral stem cell rescue, and prior external beam radiation therapy to more than 25% of active bone marrow * Patients who have received filgrastim (G-CSF) or sargramostim (GM-CSF) within 2 weeks before treatment or major surgery within the prior 4 weeks

Design outcomes

Primary

Measure	Time frame	Description
Radiographic Response Assessed by MRI or FDG-PET/MRI	Up to 2 years	Number of patients with at least a 50% reduction in tumor size on a MRI scan with stable or decreasing dose of corticosteroids

Secondary

Measure	Time frame	Description
Progression Free Survival	Up to 2 years	The number of patients without an unequivocal increase in tumor size or the appearance of new lesions by MRI
Overall Survival	Up to 2 years	The number of patients alive up to two years after treatment
Establish the Toxicity Profile of Ibritumomab Tiuxetan in This Patient Population.	Up to 30 days following the last dose of study treatment	Number of patients with toxicities related to the study drug
Dosimetry Calculations of Yttrium Y 90 Ibritumomab Tiuxetan Assessed by PET/MRI	At day 11	Number of Gy delivered to each tumor as calculated using the MIRD dosimetry formula on PET data

Countries

United States

Participant flow

Participants by arm

Arm	Count
Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan Patients receive rituximab IV on day 1. Within 7 to 9 days, patients receive rituximab IV and yttrium Y 90 ibritumomab tiuxetan IV in the absence of disease progression or unacceptable toxicity. rituximab: Given IV yttrium Y 90 ibritumomab tiuxetan: Given IV	1
Total	1

Baseline characteristics

Characteristic	Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	1 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	1 Participants
Region of Enrollment United States	1 participants
Sex: Female, Male Female	1 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 1
other Total, other adverse events	0 / 1
serious Total, serious adverse events	0 / 1

Outcome results

Primary

Radiographic Response Assessed by MRI or FDG-PET/MRI

Number of patients with at least a 50% reduction in tumor size on a MRI scan with stable or decreasing dose of corticosteroids

Time frame: Up to 2 years