Clinical trial NCT01973062: Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Primary Central Nervous System Non-Hodgkin Lymphoma
Official title: Phase II Study of Radioimmunotherapy With Zevalin (Ibritumomab Tiuxetan) Therapy for Patients With Refractory or Relapsed Primary Central Nervous System Lymphoma (PCNSL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Primary Central Nervous System Non-Hodgkin Lymphoma
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2013-10-31
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Radiographic Response Assessed by MRI or FDG-PET/MRI
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Up to 2 years
measure: Overall Survival
timeFrame: Up to 2 years
measure: Establish the Toxicity Profile of Ibritumomab Tiuxetan in This Patient Population.
timeFrame: Up to 30 days following the last dose of study treatment
measure: Dosimetry Calculations of Yttrium Y 90 Ibritumomab Tiuxetan Assessed by PET/MRI
timeFrame: At day 11
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Case Comprehensive Cancer Center
name: Manmeet Ahluwalia, MD
role: PRINCIPAL_INVESTIGATOR
References: