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| ID | Type | Description | Link |
|---|---|---|---|
| COULTER-IND-3323 | Other Grant/Funding Number | Coulter Pharmaceuticals, Inc. |
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RATIONALE: 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 transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.
PURPOSE: This phase II trial is studying how well monoclonal antibody therapy, chemotherapy, and peripheral stem cell transplant work in treating patients with relapsed or refractory non-Hodgkin's lymphoma.
OBJECTIVES:
OUTLINE: Autologous peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells or granulocyte macrophage colony-forming units. On day -19, patients receive unlabeled monoclonal antibody anti-B1 (MOAB anti-B1) IV followed by a dosimetric dose of iodine I 131 MOAB anti-B1 IV over 20 minutes. On day -12, patients receive unlabeled MOAB anti-B1 IV followed by a therapeutic dose of iodine I 131 MOAB anti-B1 IV over 20 minutes. Patients then receive high-dose chemotherapy comprising carmustine IV on day -6, etoposide IV and cytarabine IV twice daily on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous PBSC transplantation on day 0.
Patients are followed at days 30 and 100, at 6 months, and then annually thereafter.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over 5 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I | Experimental | Iodine-131 Anti-B1 Antibody/BEAM/autologous hematopoietic stem cell transplantation (AHSCT) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| carmustine | Drug | 300 mg/m2 IV on Day -6 |
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| Measure | Description | Time Frame |
|---|---|---|
| Event free survival rate | Participant survival without adverse events or progression | 100 days post transplant and at yearly intervals |
| Measure | Description | Time Frame |
|---|---|---|
| Time to treatment failure | Time from registration to time of treatment discontinuation or withdrawal for progression | time of registration to time of treatment discontinuation or withdrawal for progression |
| Overall survival |
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Inclusion Criteria:
Diagnosis of non-Hodgkin's lymphoma (NHL) of one of the following types:
Relapsed or refractory disease sensitive to initial or subsequent conventional therapy (at least a partial response)
Eligible for high-dose carmustine, etoposide, cytarabine, and melphalan protocol and autologous bone marrow transplantation or peripheral blood stem cell transplantation
Evidence of CD20 antigen expression in tumor tissue
Bidimensionally measurable disease
Adequate peripheral blood stem cells
Age: 19 to 70
Performance status: Karnofsky 70-100%
Life expectancy: at least 4 months post-transplantation
Bilirubin less than 2.0 mg/dL
Creatinine less than 2.0 mg/dL
Cardiac ejection fraction at least 40% for any of the following criteria:
DLCO at least 50% of predicted
HIV negative
Fertile patients must use effective contraception during and for at least 6 months after study participation
At least 4 weeks since prior biologic therapy and recovered
Human antimouse antibody negative
At least 4 weeks since prior cytotoxic chemotherapy and recovered
At least 4 weeks since prior radiotherapy and recovered
At least 4 weeks since prior immunosuppressants and recovered
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Julie M. Vose, MD | University of Nebraska | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UNMC Eppley Cancer Center at University of Nebraska Medical Center | Omaha | Nebraska | 68198-6805 | United States |
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| cytarabine |
| Drug |
100 mg/m2 BID on Days -5 through -2 |
|
|
| etoposide | Drug | 100 mg/m2 BID on Days -5 through -2 |
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| melphalan | Drug | 140 mg/m2 IV on Day -1 |
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|
| peripheral blood stem cell transplantation | Procedure | Following the chemotherapy, on Day 0 of treatment, the previously stored hematopoietic stem cells will be administered to the patient intravenously through a central line to the patient. |
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| tositumomab and iodine I 131 tositumomab | Radiation | Patients will receive two administrations of Iodine-131 Anti-B1 Antibody; the "dosimetric dose" and the "therapeutic dose". The dosimetric dose will consist of an infusion of unlabeled Anti-B1 Antibody (450 mg) immediately followed by an infusion of Anti-B1 Antibody (35 mg) which has been trace labeled with 5 mCi of Iodine-131 Anti-B1 Antibody. Using whole body anterior and posterior gamma camera scans and serial imaging studies over approximately one week, the clearance of the whole body dosimetric dose will be used to calculate the subsequent therapeutic dose of Iodine-131 Anti-B1 Antibody which delivers a total body dose of 75 cGy to the subject |
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Time from first participant enrollment to last participant death or end of study
| Time from registration to last participant death |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D008228 | Lymphoma, Non-Hodgkin |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D016400 | Lymphoma, Large-Cell, Immunoblastic |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D016393 | Lymphoma, B-Cell |
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| ID | Term |
|---|---|
| D002330 | Carmustine |
| D003561 | Cytarabine |
| D005047 | Etoposide |
| C061400 | etoposide phosphate |
| D008558 | Melphalan |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| C119496 | tositumomab I-131 |
| ID | Term |
|---|---|
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D009603 | Nitroso Compounds |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
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