Clinical trial NCT00031642: Monoclonal Antibody Therapy in Relapsed Non-Hodgkin's After Chemotherapy and Autologous Stem Cell Transplantation
Official title: Phase I/II Study of IDEC-Y2B8 (Zevalin) for Post Transplant Relapses of B-Cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult Burkitt lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: Biogen
First posted: 2003-01-27
Enrollment: 26
Sex: ALL
Minimum age (years): 19
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and deliver cancer-killing substances to them without harming normal cells. Radiolabeled monoclonal antibodies can locate and deliver radioactive cancer-killing substances.

PURPOSE: Phase I/II trial to study the effectiveness of combining radiolabeled monoclonal antibodies with rituximab in treating patients who have non-Hodgkin's lymphoma that has not responded to high-dose chemotherapy and autologous stem cell transplantation.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of yttrium Y 90-labeled ibritumomab tiuxetan when administered with rituximab in patients with B-cell non-Hodgkin's lymphoma who have relapsed after high-dose chemotherapy and autologous hematopoietic stem cell transplantation.
* Determine the safety and efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study of yttrium Y 90-labeled ibritumomab tiuxetan (IDEC-Y2B8).

* Phase I: Patients receive rituximab IV over 4-6 hours followed by indium In 111-labeled ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0. Patients receive rituximab IV again on day 7 followed by IDEC-Y2B8 IV over 10 minutes.

Cohorts of 3-6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 3 of 6 patients experience dose-limiting toxicity.

* Phase II: Once the MTD is determined, 58 additional patients are treated at that dose level as in phase I.

Patients are followed at 6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 78 patients (20 for phase I and 58 for phase II) will be accrued for this study within 2 years.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of relapsed B-cell non-Hodgkin's lymphoma (NHL) after high-dose chemotherapy and autologous stem cell transplantation
* Less than 25% bone marrow involvement with NHL as evidenced by unilateral or bilateral biopsy within the past 6 weeks

  o Bone marrow biopsy should demonstrate 15-20% of cellular space occupied by normal hematopoiesis
* CD20 antigen expression in tumor tissue within the past year as evidenced by 1 of the following:

  * Immunoperoxidase stains of tissue showing positive reactivity with L26 antibody
  * Flow cytometry studies
* Measurable disease

  o More than 2 cm bidimensionally
* 19 years of age and over
* Performance status WHO 0-2
* Life expectancy at least 3 months
* Absolute neutrophil count greater than 1,500/mm\^3
* Platelet count greater than 150,000/mm\^3
* Bilirubin less than 2.0 mg/dL
* SGOT or SGPT no greater than 2.5 times upper limit of normal (unless due to lymphomatous infiltration of the liver)
* Creatinine less than 2.0 mg/dL
* Fertile patients must use effective contraception during and for 6 months after study therapy
* HIV negative
* At least 4 weeks since prior growth factors
* At least 4 weeks since prior biologic therapy
* At least 4 weeks since any prior cytotoxic chemotherapy (6 weeks for nitrosoureas)
* At least 4 weeks since prior radiotherapy
* Recovered from all prior therapy
* At least 4 weeks since prior immunosuppressants

Exclusion Criteria:

* No active CNS lymphoma
* No HIV- or AIDS-related lymphoma
* No transfusion dependency
* No active obstructive hydronephrosis
* Not pregnant or nursing/negative pregnancy test
* No active infection requiring oral or IV antibiotics
* No human antimurine antibody positivity
* No other major medical problems
* No dependency on hematopoietic growth factors (e.g., epoetin alfa, interleukin-11, filgrastim \[G-CSF\], or sargramostim \[GM-CSF\])
* No prior radioimmunotherapy
* No other concurrent biologic therapy of any kind
* No prior fludarabine
* No concurrent chemotherapy
* No concurrent steroids except as maintenance for non-cancerous disease
* No prior pelvic radiotherapy
* No prior radiotherapy to more than 25% of estimated bone marrow reserve
* No concurrent external beam radiotherapy
* No other concurrent investigational drugs
* No other concurrent anti-cancer therapy

Primary outcomes:
measure: Maximum tolerated dose
measure: Safety and efficacy
Secondary outcomes:
Other outcomes:
Locations:
city: Omaha
country: United States
facility: Eppley Cancer Center at University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Julie M Vose, MD
role: STUDY_CHAIR
References: