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Radiolabeled Monoclonal Antibody Therapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Lymphoma or Waldenstrom's Macroglobulinemia

This study is ongoing, but not recruiting participants.

Sponsors and Collaborators: Garden State Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004107
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Drug: filgrastim
Drug: indium In 111 monoclonal antibody MN-14
Drug: yttrium Y 90 humanized epratuzumab
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Phase I
Phase II

Genetics Home Reference related topics:   aceruloplasminemia    hemophilia   

MedlinePlus related topics:   Bone Marrow Transplantation    Cancer    Leukemia, Adult Acute    Leukemia, Adult Chronic    Lymphoma   

Drug Information available for:   Filgrastim    Epratuzumab    Yttrium Y 90 Epratuzumab   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment
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

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:   February 1998

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
Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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

  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004107

Locations
United States, New Jersey
Garden State Cancer Center    
      Belleville, New Jersey, United States, 07103
St. Barnabas Medical Center    
      Livingston, New Jersey, United States, 07039
St. Joseph's Hospital and Medical Center    
      Paterson, New Jersey, United States, 07503
United States, Pennsylvania
University of Pennsylvania Cancer Center    
      Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators
Garden State Cancer Center
National Cancer Institute (NCI)

Investigators
Study Chair:     Jack D. Burton, MD     Garden State Cancer Center    
  More Information


Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   CDR0000067327, CMMI-C-037B-97, UPCC-1499, NCI-H99-0040
First Received:   December 10, 1999
Last Updated:   July 23, 2008
ClinicalTrials.gov Identifier:   NCT00004107
Health Authority:   United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Study placed in the following topic categories:
Leukemia, Lymphoid
Blood Protein Disorders
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Paraproteinemias
Hemostatic Disorders
Lymphoma, large-cell, immunoblastic
Acute lymphoblastic leukemia, adult
Antibodies, Monoclonal
Lymphoma, large-cell
Lymphoma, B-Cell
Burkitt's lymphoma
Leukemia
Hemorrhagic Disorders
Lymphoma, Large-Cell, Immunoblastic
Waldenstrom macroglobulinemia
Lymphoma
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, B-cell, chronic
Blood Coagulation Disorders
Vascular Diseases
Lymphoblastic lymphoma
Mantle cell lymphoma
Recurrence

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Immunologic Factors
Immune System Diseases
Physiological Effects of Drugs
Cardiovascular Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 30, 2008




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