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

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
filgrastim
autologous bone marrow transplantation
peripheral blood stem cell transplantation
indium In 111 monoclonal antibody MN-14
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, 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

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Garden State Cancer Center
  • St. Barnabas Medical Center
  • St. Joseph's Hospital and Medical Center
  • University of Pennsylvania Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
December 10, 1999
Last Updated
June 21, 2011
Sponsor
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00004107
Brief Title
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

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
February 1998 (undefined)
Primary Completion Date
May 2001 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Garden State Cancer Center at the Center for Molecular Medicine and Immunology
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Description
as prescribed by physician
Intervention Type
Procedure
Intervention Name(s)
autologous bone marrow transplantation
Intervention Description
1-2 weeks before treatment
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Description
1-2 weeks before treatment
Intervention Type
Radiation
Intervention Name(s)
indium In 111 monoclonal antibody MN-14
Intervention Description
intravenous infusion over 30 min; single dose
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 epratuzumab
Intervention Description
intravenous infusion over 30 min; single dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
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
Facility Name
St. Barnabas Medical Center
City
Livingston
State/Province
New Jersey
ZIP/Postal Code
07039
Country
United States
Facility Name
St. Joseph's Hospital and Medical Center
City
Paterson
State/Province
New Jersey
ZIP/Postal Code
07503
Country
United States
Facility Name
University of Pennsylvania Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

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

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