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

• ClinicalTrials.gov Identifier: NCT00004107
• Recruitment Status: Completed
• First Posted: April 16, 2004
• Last Update Posted: June 22, 2011
• Sponsor: Garden State Cancer Center at the Center for Molecular Medicine and Immunology
• Collaborator: National Cancer Institute (NCI)
• Information provided by: Garden State Cancer Center at the Center for Molecular Medicine and Immunology

Tracking Information

• First Submitted Date: December 10, 1999
• First Posted Date: April 16, 2004
• Last Update Posted Date: June 22, 2011
• Study Start Date: February 1998
• Actual Primary Completion Date: May 2001 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Leukemia
• Lymphoma

Intervention

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

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: June 21, 2011): 18
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Actual Primary Completion Date: May 2001 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00004107
• Other Study ID Numbers: CDR0000067327; R01CA067026 ( U.S. NIH Grant/Contract ); CMMI-C-037B-97; UPCC-1499; NCI-H99-0040
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Robert M Sharkey, GSCC
• Study Sponsor: Garden State Cancer Center at the Center for Molecular Medicine and Immunology
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Jack D. Burton, MD; Garden State Cancer Center at the Center for Molecular Medicine and Immunology

• PRS Account: Garden State Cancer Center at the Center for Molecular Medicine and Immunology
• Verification Date: June 2011