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Radiolabeled Monoclonal Antibody, Combination Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With Recurrent or Refractory B-Cell Cancer

This study is ongoing, but not recruiting participants.

Sponsored by: Garden State Cancer Center
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004086
  Purpose

RATIONALE: Radiolabeled monoclonal antibodies can locate cancer cells and either kill them or deliver cancer killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody plus combination chemotherapy and peripheral stem cell transplantation in treating patients who have recurrent or B-cell cancer.


Condition Intervention Phase
Leukemia
Lymphoma
Drug: cisplatin
Drug: cytarabine
Drug: etoposide
Drug: filgrastim
Drug: ifosfamide
Drug: indium In 111 LL2 IgG
Drug: yttrium Y 90 humanized epratuzumab
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Phase I

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

Drug Information available for:   Ifosfamide    Filgrastim    Cytarabine    Cytarabine hydrochloride    Etoposide    Cisplatin    Etoposide phosphate    Epratuzumab    Yttrium Y 90 Epratuzumab   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment
Official Title:   A Phase I Trial of a Combined Regimen of Chemotherapy and 90Y-Labeled, Humanized LL2 (Anti-CD22) Antibody With Peripheral Stem Cell Rescue for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma

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

Study Start Date:   June 1997

Detailed Description:

OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of yttrium Y 90 humanized anti-CD22 LL2 (Y90 MOAB hLL2) in combination with salvage chemotherapy and autologous peripheral blood stem cell rescue in patients with recurrent or refractory B-cell malignancies. II. Study the effect of chemotherapy on the uptake of Y90 MOAB hLL2 into tumor sites and normal organs by pretherapy imaging using indium In 111 humanized LL2 and intratherapy imaging. III. Determine the extent and duration of tumor response in patients receiving this regimen.

OUTLINE: This is a dose escalation study of yttrium Y 90 humanized anti-CD22 monoclonal antibody LL2 (Y90 MOAB hLL2). Patients receive filgrastim (G-CSF) subcutaneously daily for 5 days and undergo harvest of peripheral blood stem cells (PBSC) on 2 or more consecutive days. If an adequate number of CD34+ cells are not harvested, autologous bone marrow may be used. Chemotherapy-induced mobilization with filgrastim allowed. Patients undergo pretherapy imaging with indium In 111 humanized LL2 (In111 hLL2) for up to 40 minutes on day -7. Patients receive Y90 MOAB hLL2 for up to 40 minutes on day 0 plus In111 hLL2, followed by Y90 MOAB hLL2 alone on day 3. Patients receive ifosfamide IV over 1 hour, cisplatin IV over 2 hours, and cytarabine IV over 2 hours on days 1 and 4. Oral etoposide is given daily on days 1-7. PBSC or bone marrow is reinfused on days 9-14, depending on MOAB clearance. 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 3 or 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: Approximately 15-24 patients will be accrued for this study within 2-2.5 years.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed recurrent or refractory B-cell malignancy that has failed at least one standard therapy Stage II to IV non-Hodgkin's lymphoma B-cell chronic lymphocytic leukemia, hairy cell leukemia, or Waldenstrom's macroglobulinemia allowed if: Autologous bone marrow or peripheral blood stem cells (PBSC) with no greater than 5% tumor involvement available Estimated radiation dose to marrow no greater than 3,000 cGy (bone marrow involvement of greater than 25% is allowed provided stem cell contamination and predicted marrow radiation doses are below the above cited cut off values) At least 1 confirmed site of tumor targeted by pretherapy indium In 111 humanized LL2 Autologous peripheral blood stem cells (PBSC) or bone marrow available No active brain metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Karnofsky 70-100% 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 less than 2 mg/dL Renal: Creatinine less than 1.5 times upper limit of normal Cardiovascular: Cardiac ejection fraction greater than 50% Pulmonary: DLCO greater than 60% predicted Forced vital capacity greater than 60% predicted Other: No severe anorexia, nausea, or vomiting HIV negative No prisoners No concurrent significant medical complication that would preclude study compliance Not pregnant Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior low dose radioimmunotherapy allowed Chemotherapy: No prior high dose chemotherapy with PBSC rescue At least 4 weeks since prior chemotherapy and recovered Endocrine therapy: At least 2 weeks since prior corticosteroids and recovered Radiotherapy: Prior low dose radioimmunotherapy allowed Prior radiotherapy to less than 35% of red marrow allowed At least 4 weeks since prior radiotherapy to index lesion Surgery: At least 4 weeks since major surgery

  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004086

Locations
United States, New Jersey
Garden State Cancer Center    
      Belleville, New Jersey, United States, 07103

Sponsors and Collaborators
Garden State Cancer Center

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:   CDR0000067298, CMMI-C-037C-97, NCI-V99-1569
First Received:   December 10, 1999
Last Updated:   July 23, 2008
ClinicalTrials.gov Identifier:   NCT00004086
Health Authority:   United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
Waldenstrom macroglobulinemia  
refractory chronic lymphocytic leukemia  
B-cell chronic lymphocytic leukemia  
refractory hairy cell 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
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Lymphoma, B-Cell, Marginal Zone
Etoposide phosphate
Lymphoma, large-cell, immunoblastic
Antibodies, Monoclonal
Lymphoma, B-Cell
Lymphoma, large-cell
Burkitt's lymphoma
Leukemia
Cisplatin
Lymphoma, Large-Cell, Immunoblastic
Waldenstrom macroglobulinemia
Etoposide
Lymphoma
Cytarabine
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Leukemia, B-cell, chronic
Lymphoblastic lymphoma
Mantle cell lymphoma
Recurrence
Lymphatic Diseases
Antibodies
Ifosfamide
Waldenstrom Macroglobulinemia
Leukemia, Hairy Cell

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on November 20, 2008




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