Clinical trial NCT00004107: Radiolabeled Monoclonal Antibody Therapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Lymphoma or Waldenstrom's Macroglobulinemia
Official title: Phase I/II Radioimmunotherapy of Non-Hodgkin's Lymphoma With High-Dose 90Y-Labeled Humanized LL2 Anti-CD-22 Antibody and Peripheral Blood Stem Cell Rescue
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia
Lymphoma
Keywords: Waldenstrom macroglobulinemia
recurrent adult acute lymphoblastic leukemia
refractory chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia
B-cell adult acute lymphoblastic leukemia
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
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: Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
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. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by monoclonal antibody therapy used to kill cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of radiolabeled monoclonal antibody therapy plus peripheral stem cell transplantation in treating patients who have lymphoma or Waldenstrom's macroglobulinemia that has not responded to previous therapy.

Detailed description: OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of radioimmunotherapy using high dose yttrium Y 90 humanized anti-CD22 monoclonal antibody LL2 (Y90 MOAB hLL2) followed by autologous peripheral blood stem cell transplantation in patients with B cell lymphomas or Waldenstrom's macroglobulinemia. II. Determine the organ and tumor dosimetry for comparison to clinical measurement of toxicity and antitumor responses in these patients. III. Determine magnitude and duration of human anti-humanized LL2 antibody (HAhLL2) or anti-DOTA response in these patients. IV. Evaluate the extent and duration of antitumor response to this regimen in these patients.

OUTLINE: This is a dose escalation, multicenter study. Patients are stratified according to prior treatment (high dose chemotherapy with transplantation vs low dose chemotherapy with radioimmunotherapy (RAIT) vs low dose chemotherapy without RAIT). Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 5 days and undergo harvest of peripheral blood stem cells (PBSC). If an adequate number of CD34+ cells are not harvested, autologous bone marrow may be used. Patients undergo pretherapy imaging with indium In 111 monoclonal antibody MN-14 (In111-MN-14) IV on day -7. If at least 1 tumor site is targeted, patients receive high dose yttrium Y 90 humanized anti-CD22 monoclonal antibody LL2 (Y90 MOAB hLL2) IV for up to 50 minutes on day 0. PBSC or bone marrow is reinfused approximately 7-14 days following infusion of Y90 MOAB hLL2. Patients also receive G-CSF SC daily until 3 days after blood counts have recovered. Cohorts of 3-6 patients receive escalating doses of Y90 MOAB hLL2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are followed weekly for 2 months, monthly for 6 months, and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically or cytologically proven B cell lymphoma of one of the following types: Any histologic grade of non-Hodgkin's lymphoma Chronic lymphocytic leukemia CD22 positive acute lymphocytic leukemia Waldenstrom's macroglobulinemia Must have failed at least 1 standard therapy Autologous peripheral blood stem cells (PBSC) or bone marrow available Bone marrow involvement allowed if: Autologous bone marrow or PBSC with no greater than 5% tumor involvement available Radiation dose to marrow no greater than 3,000 cGy until 6 patients have been safely treated at that dose level At least 1 confirmed site of tumor targeted by pretherapy indium In 111 monoclonal antibody MN-14 imaging No brain metastases

PATIENT CHARACTERISTICS: Age: 18 to 80 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 2.0 mg/dL AST and alkaline phosphatase less than 1.5 times upper limit of normal (ULN) in the absence of bone involvement Renal: Creatinine less than 1.5 times ULN Cardiovascular: Ejection fraction at least 50% Pulmonary: DLCO at least 60% of predicted Forced vital capacity at least 60% of predicted Other: No severe anorexia, nausea, or vomiting No concurrent significant medical complications that would preclude study participation Not pregnant Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior radioimmunotherapy AND high dose chemotherapy Chemotherapy: No prior high dose chemotherapy AND radioimmunotherapy At least 4 weeks since other prior chemotherapy and recovered Endocrine therapy: At least 2 weeks since prior corticosteroids and recovered Radiotherapy: No prior radioimmunotherapy AND high dose chemotherapy At least 4 weeks since prior radiotherapy to index lesion No prior radiotherapy to greater than 25% of any critical organ (e.g., lung, liver, kidneys) No prior total body irradiation Surgery: At least 4 weeks since prior major surgery

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Belleville
country: United States
facility: Garden State Cancer Center
state: New Jersey
city: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hospital and Medical 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: