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	Treatment or Intervention	Phase
recurrent diffuse small lymphocytic/marginal zone lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult lymphoblastic lymphoma recurrent grade III follicular large cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult diffuse small noncleaved cell/Burkitt's lymphoma recurrent adult diffuse mixed cell lymphoma recurrent mantle cell lymphoma refractory chronic lymphocytic leukemia recurrent adult diffuse large cell lymphoma Waldenstrom's Macroglobulinemia recurrent adult acute lymphoblastic leukemia recurrent grade I follicular small cleaved cell lymphoma B-cell Chronic Lymphocytic Leukemia recurrent grade II follicular mixed cell lymphoma B-cell adult acute lymphoblastic leukemia	Drug: filgrastim  Drug: indium In 111 monoclonal antibody MN-14  Drug: yttrium Y 90 humanized monoclonal antibody LL2	Phase I Phase II

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years   -   80 Years

Criteria

PROTOCOL ENTRY 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

--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

--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

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

Study chairs or principal investigators

Jack D. Burton,  Study Chair,  Garden State Cancer Center   

Study ID Numbers:  CDR0000067327; CMMI-C-037B-97; NCI-H99-0040; UPCC-1499
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004107
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08