Clinical trial NCT00004084: Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Lymphoma or Leukemia
Official title: Phase I/II Radioimmunotherapy of Non-Hodgkin's Lymphoma With Radiolabeled Humanized Immu-LL2: Treatment With 90Y-hLL2 IgG
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia
Lymphoma
Keywords: stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
refractory chronic lymphocytic leukemia
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage I adult lymphoblastic lymphoma
stage I adult Burkitt lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
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 lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II mantle cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
contiguous stage II marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage I marginal zone lymphoma
stage I small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-15
Enrollment: 21
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: RATIONALE: Radiolabeled monoclonal antibodies can locate cancer cells and deliver cancer-killing substances to them without harming normal cells.

PURPOSE: Phase I/II trial to study the effectiveness of radiolabeled monoclonal antibody therapy in treating patients who have lymphoma or leukemia that has not responded to previous chemotherapy.

Detailed description: OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of yttrium Y 90-labeled humanized anti-CD22 monoclonal antibody LL2(90Y-hLL2 IgG) in patients with B-cell malignancies. II. Determine the pharmacokinetics and biodistribution of indium In 111 humanized LL2 (111In-hLL2 IgG) in these patients. III. Evaluate the immunogenicity of repeated injections of 90Y-hLL2 IgG in these patients. IV. Determine whether 90Y-hLL2 IgG versus indium In 131 humanized LL2 IgG has a therapeutic advantage based on organ and tumor dosimetry obtained with 111In-hLL2 IgG.

OUTLINE: This is a dose escalation study. Patients are stratified into risk groups (high vs low). Patients receive pretherapy imaging with indium In 111 humanized LL2 IgG IV for up to 30 minutes on days -7 to 0. Patients receive yttrium Y 90-labeled humanized anti-CD22 monoclonal antibody LL2 (90Y-hLL2-IgG) IV for up to 30 minutes on day 0. Cohorts of 3-6 patients receive escalating doses of 90Y-hLL2-IgG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding the dose at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity. Patients are followed every 2 weeks for 1 month, monthly for 2 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study within 1-2 years.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically or cytologically confirmed B-cell malignancy, including B-cell non-Hodgkin's lymphoma or B-cell chronic lymphocytic leukemia, that has failed at least one regimen of standard chemotherapy At least 1 confirmed tumor site by radiolabeled LL2 IgG No greater than 25% bone or bone marrow involvement No brain metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2 mg/dL AST and alkaline phosphatase less than 1.5 times upper limit of normal (ULN) (except for bone involvement) Renal: Creatinine less than 1.5 times ULN Other: Not pregnant Fertile patients must use effective contraception during and for 3-6 months after study HIV negative No severe anorexia, nausea, or vomiting No other significant concurrent medical condition that would interfere with compliance

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior murine monoclonal antibody therapy allowed (if unreactive to yttrium Y 90-labeled humanized anti-CD22 monoclonal antibody LL2 by HPLC or ELISA test) Chemotherapy: At least 4 weeks since prior chemotherapy Endocrine therapy: At least 2 weeks since prior corticosteroids (except for adrenal insufficiency) Radiotherapy: At least 4 weeks since prior radiotherapy to the index lesion No prior extensive radiotherapy to greater than 25% of bone marrow (except total body irradiation as part of bone marrow or stem cell transplantation regimen with engraftment of functional marrow (i.e., producing normal peripheral blood counts) No prior maximum tolerated dose levels of radiotherapy to critical organs (e.g., lung, liver, or kidney) Surgery: At least 4 weeks since prior major surgery Other: No other concurrent investigational agents

Primary outcomes:
measure: maximum tolerated dose
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Belleville
country: United States
facility: Garden State Cancer Center
state: New Jersey
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
Study officials:
affiliation: Garden State Cancer Center at the Center for Molecular Medicine and Immunology
name: Jack D. Burton, MD
role: STUDY_CHAIR
References: