A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma

Robert T O'Donnell, S. Shen, S. J. Denardo, Theodore Wun, D. L. Kukis, D. S. Goldstein, Gerald L Denardo

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Prior clinical trials proved that all histologic grades of chemotherapy-resistant B-cell non-Hodgkin's lymphoma (NHL) could respond to radio-immunotherapy (RIT) with 131I-Lym- 1 and 67Cu-2IT-BAT-Lym-1. This Phase I study was conducted to determine the safety and maximum tolerated dose (MTD) of 90Y-2IT-BAD-Lym-1. Methods: Lym-1 is a mouse monoclonal antibody that preferentially targets malignant B-lymphocytes. 90Y has β emissions suitable for therapy but no gamma emissions, therefore, 111In-2IT-BAD-Lym-1 is used for imaging. The macrocyclic chelator, DOTA, bound 90Y tightly to form a stable drug. Patients with chemotherapy-resistant NHL received 90Y-2IT-BAD-Lym-1 at administered doses of: 0.185, 0.278, or 0.370 GBq/m2. Results. Myelotoxicity, especially thrombocytopenia, was dose-limiting. No significant non-hematologic toxicity occurred. Human anti-mouse antibody (HAMA) developed in 3/8 patients. The mean radiation dose to the 33 imaged tumors was 7.0 Gy/GBq. Lung, kidney and liver received mean radiation doses of 1.3, 2.4, and 6.4 Gy/GBq, respectively from 90Y-2IT-BAD-Lym-1. The tumor: body and tumor:bone marrow (by imaging) ratios were 16.4:1 and 5.8:1, respectively. In this Phase I study, 5/8 patients that failed prior chemotherapy had a partial response or stabilization of NHL after RIT. Conclusion: The safety and toxicity of 90Y-2IT-BAD- Lym-1 were determined and the MTD was 0.370 GBq/m2 a dose used in 4 patients. 90Y-2IT-BAD- Lym-1 may be useful for future clinical trials because 90Y is readily available and can deliver potent β emissions to NHL. Bone marrow support however, will be required for further dose escalation.

Original languageEnglish (US)
Pages (from-to)3647-3655
Number of pages9
JournalAnticancer Research
Volume20
Issue number5 C
StatePublished - 2000

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Non-Hodgkin's Lymphoma
Maximum Tolerated Dose
Radio
Drug Therapy
Immunotherapy
Bone Marrow
Clinical Trials
Radiation
Safety
Neoplasms
B-Cell Lymphoma
Chelating Agents
Thrombocytopenia
2IT-BAD-Lym-1 monoclonal antibody
Anti-Idiotypic Antibodies
B-Lymphocytes
Monoclonal Antibodies
Kidney
Lung
Liver

Keywords

  • Antibody
  • Immunotherapy
  • Lym-1
  • Lymphoma
  • Radiation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma. / O'Donnell, Robert T; Shen, S.; Denardo, S. J.; Wun, Theodore; Kukis, D. L.; Goldstein, D. S.; Denardo, Gerald L.

In: Anticancer Research, Vol. 20, No. 5 C, 2000, p. 3647-3655.

Research output: Contribution to journalArticle

O'Donnell, RT, Shen, S, Denardo, SJ, Wun, T, Kukis, DL, Goldstein, DS & Denardo, GL 2000, 'A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma', Anticancer Research, vol. 20, no. 5 C, pp. 3647-3655.
O'Donnell RT, Shen S, Denardo SJ, Wun T, Kukis DL, Goldstein DS et al. A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma. Anticancer Research. 2000;20(5 C):3647-3655.
O'Donnell, Robert T ; Shen, S. ; Denardo, S. J. ; Wun, Theodore ; Kukis, D. L. ; Goldstein, D. S. ; Denardo, Gerald L. / A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma. In: Anticancer Research. 2000 ; Vol. 20, No. 5 C. pp. 3647-3655.
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abstract = "BACKGROUND: Prior clinical trials proved that all histologic grades of chemotherapy-resistant B-cell non-Hodgkin's lymphoma (NHL) could respond to radio-immunotherapy (RIT) with 131I-Lym- 1 and 67Cu-2IT-BAT-Lym-1. This Phase I study was conducted to determine the safety and maximum tolerated dose (MTD) of 90Y-2IT-BAD-Lym-1. Methods: Lym-1 is a mouse monoclonal antibody that preferentially targets malignant B-lymphocytes. 90Y has β emissions suitable for therapy but no gamma emissions, therefore, 111In-2IT-BAD-Lym-1 is used for imaging. The macrocyclic chelator, DOTA, bound 90Y tightly to form a stable drug. Patients with chemotherapy-resistant NHL received 90Y-2IT-BAD-Lym-1 at administered doses of: 0.185, 0.278, or 0.370 GBq/m2. Results. Myelotoxicity, especially thrombocytopenia, was dose-limiting. No significant non-hematologic toxicity occurred. Human anti-mouse antibody (HAMA) developed in 3/8 patients. The mean radiation dose to the 33 imaged tumors was 7.0 Gy/GBq. Lung, kidney and liver received mean radiation doses of 1.3, 2.4, and 6.4 Gy/GBq, respectively from 90Y-2IT-BAD-Lym-1. The tumor: body and tumor:bone marrow (by imaging) ratios were 16.4:1 and 5.8:1, respectively. In this Phase I study, 5/8 patients that failed prior chemotherapy had a partial response or stabilization of NHL after RIT. Conclusion: The safety and toxicity of 90Y-2IT-BAD- Lym-1 were determined and the MTD was 0.370 GBq/m2 a dose used in 4 patients. 90Y-2IT-BAD- Lym-1 may be useful for future clinical trials because 90Y is readily available and can deliver potent β emissions to NHL. Bone marrow support however, will be required for further dose escalation.",
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T1 - A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma

AU - O'Donnell, Robert T

AU - Shen, S.

AU - Denardo, S. J.

AU - Wun, Theodore

AU - Kukis, D. L.

AU - Goldstein, D. S.

AU - Denardo, Gerald L

PY - 2000

Y1 - 2000

N2 - BACKGROUND: Prior clinical trials proved that all histologic grades of chemotherapy-resistant B-cell non-Hodgkin's lymphoma (NHL) could respond to radio-immunotherapy (RIT) with 131I-Lym- 1 and 67Cu-2IT-BAT-Lym-1. This Phase I study was conducted to determine the safety and maximum tolerated dose (MTD) of 90Y-2IT-BAD-Lym-1. Methods: Lym-1 is a mouse monoclonal antibody that preferentially targets malignant B-lymphocytes. 90Y has β emissions suitable for therapy but no gamma emissions, therefore, 111In-2IT-BAD-Lym-1 is used for imaging. The macrocyclic chelator, DOTA, bound 90Y tightly to form a stable drug. Patients with chemotherapy-resistant NHL received 90Y-2IT-BAD-Lym-1 at administered doses of: 0.185, 0.278, or 0.370 GBq/m2. Results. Myelotoxicity, especially thrombocytopenia, was dose-limiting. No significant non-hematologic toxicity occurred. Human anti-mouse antibody (HAMA) developed in 3/8 patients. The mean radiation dose to the 33 imaged tumors was 7.0 Gy/GBq. Lung, kidney and liver received mean radiation doses of 1.3, 2.4, and 6.4 Gy/GBq, respectively from 90Y-2IT-BAD-Lym-1. The tumor: body and tumor:bone marrow (by imaging) ratios were 16.4:1 and 5.8:1, respectively. In this Phase I study, 5/8 patients that failed prior chemotherapy had a partial response or stabilization of NHL after RIT. Conclusion: The safety and toxicity of 90Y-2IT-BAD- Lym-1 were determined and the MTD was 0.370 GBq/m2 a dose used in 4 patients. 90Y-2IT-BAD- Lym-1 may be useful for future clinical trials because 90Y is readily available and can deliver potent β emissions to NHL. Bone marrow support however, will be required for further dose escalation.

AB - BACKGROUND: Prior clinical trials proved that all histologic grades of chemotherapy-resistant B-cell non-Hodgkin's lymphoma (NHL) could respond to radio-immunotherapy (RIT) with 131I-Lym- 1 and 67Cu-2IT-BAT-Lym-1. This Phase I study was conducted to determine the safety and maximum tolerated dose (MTD) of 90Y-2IT-BAD-Lym-1. Methods: Lym-1 is a mouse monoclonal antibody that preferentially targets malignant B-lymphocytes. 90Y has β emissions suitable for therapy but no gamma emissions, therefore, 111In-2IT-BAD-Lym-1 is used for imaging. The macrocyclic chelator, DOTA, bound 90Y tightly to form a stable drug. Patients with chemotherapy-resistant NHL received 90Y-2IT-BAD-Lym-1 at administered doses of: 0.185, 0.278, or 0.370 GBq/m2. Results. Myelotoxicity, especially thrombocytopenia, was dose-limiting. No significant non-hematologic toxicity occurred. Human anti-mouse antibody (HAMA) developed in 3/8 patients. The mean radiation dose to the 33 imaged tumors was 7.0 Gy/GBq. Lung, kidney and liver received mean radiation doses of 1.3, 2.4, and 6.4 Gy/GBq, respectively from 90Y-2IT-BAD-Lym-1. The tumor: body and tumor:bone marrow (by imaging) ratios were 16.4:1 and 5.8:1, respectively. In this Phase I study, 5/8 patients that failed prior chemotherapy had a partial response or stabilization of NHL after RIT. Conclusion: The safety and toxicity of 90Y-2IT-BAD- Lym-1 were determined and the MTD was 0.370 GBq/m2 a dose used in 4 patients. 90Y-2IT-BAD- Lym-1 may be useful for future clinical trials because 90Y is readily available and can deliver potent β emissions to NHL. Bone marrow support however, will be required for further dose escalation.

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KW - Immunotherapy

KW - Lym-1

KW - Lymphoma

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