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 language | English (US) |
|---|---|
| Pages (from-to) | 3647-3655 |
| Number of pages | 9 |
| Journal | Anticancer Research |
| Volume | 20 |
| Issue number | 5 C |
| State | Published - 2000 |
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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 journal › Article
}
TY - JOUR
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.
KW - Antibody
KW - Immunotherapy
KW - Lym-1
KW - Lymphoma
KW - Radiation
UR - http://www.scopus.com/inward/record.url?scp=0034532254&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034532254&partnerID=8YFLogxK
M3 - Article
C2 - 11268433
AN - SCOPUS:0034532254
VL - 20
SP - 3647
EP - 3655
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 5 C
ER -