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

Primary Purpose

Leukemia, Lymphoma

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
filgrastim
cisplatin
cytarabine
etoposide
ifosfamide
autologous bone marrow transplantation
peripheral blood stem cell transplantation
indium In 111 LL2 IgG
yttrium Y 90 epratuzumab
Sponsored by
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Garden State Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
December 10, 1999
Last Updated
June 6, 2009
Sponsor
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
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1. Study Identification

Unique Protocol Identification Number
NCT00004086
Brief Title
Radiolabeled Monoclonal Antibody, Combination Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With Recurrent or Refractory B-Cell Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2001
Overall Recruitment Status
Unknown status
Study Start Date
June 1997 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Garden State Cancer Center at the Center for Molecular Medicine and Immunology

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Intervention Type
Procedure
Intervention Name(s)
autologous bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Type
Radiation
Intervention Name(s)
indium In 111 LL2 IgG
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 epratuzumab

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jack D. Burton, MD
Organizational Affiliation
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Official's Role
Study Chair
Facility Information:
Facility Name
Garden State Cancer Center
City
Belleville
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States

12. IPD Sharing Statement

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

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