Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non-Hodgkin's lymphoma

Thomas Elmer Witzig, Christine A. White, Gregory A. Wiseman, Leo I. Gordon, Christos Emmanouilides, Andrew Raubitschek, Nalini Janakiraman, John Gutheil, Russell J. Schilder, Stewart Spies, Daniel H S Silverman, Elizabeth Parker, Antonio J. Grillo-López

Research output: Contribution to journalArticle

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Abstract

Purpose: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy. Patients and Methods: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20+ B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass ≥ 5 cm. Results: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/μL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (≥ 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2%) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody). Conclusion: These phase I/II data demonstrate that IDEC-Y2B8 rodioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.

Original languageEnglish (US)
Pages (from-to)3793-3803
Number of pages11
JournalJournal of Clinical Oncology
Volume17
Issue number12
StatePublished - Dec 1999

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Radioimmunotherapy
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Maximum Tolerated Dose
Antibodies
Yttrium Radioisotopes
Platelet Count
B-Lymphocytes
Therapeutics
Mantle-Cell Lymphoma
Pentetic Acid
Anthracyclines
Splenomegaly
Kaplan-Meier Estimate
Complementary Therapies
Antibody Formation
Disease Progression
ibritumomab tiuxetan
Immunoglobulins
Anti-Idiotypic Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Witzig, T. E., White, C. A., Wiseman, G. A., Gordon, L. I., Emmanouilides, C., Raubitschek, A., ... Grillo-López, A. J. (1999). Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non-Hodgkin's lymphoma. Journal of Clinical Oncology, 17(12), 3793-3803.

Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non-Hodgkin's lymphoma. / Witzig, Thomas Elmer; White, Christine A.; Wiseman, Gregory A.; Gordon, Leo I.; Emmanouilides, Christos; Raubitschek, Andrew; Janakiraman, Nalini; Gutheil, John; Schilder, Russell J.; Spies, Stewart; Silverman, Daniel H S; Parker, Elizabeth; Grillo-López, Antonio J.

In: Journal of Clinical Oncology, Vol. 17, No. 12, 12.1999, p. 3793-3803.

Research output: Contribution to journalArticle

Witzig, TE, White, CA, Wiseman, GA, Gordon, LI, Emmanouilides, C, Raubitschek, A, Janakiraman, N, Gutheil, J, Schilder, RJ, Spies, S, Silverman, DHS, Parker, E & Grillo-López, AJ 1999, 'Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non-Hodgkin's lymphoma', Journal of Clinical Oncology, vol. 17, no. 12, pp. 3793-3803.
Witzig, Thomas Elmer ; White, Christine A. ; Wiseman, Gregory A. ; Gordon, Leo I. ; Emmanouilides, Christos ; Raubitschek, Andrew ; Janakiraman, Nalini ; Gutheil, John ; Schilder, Russell J. ; Spies, Stewart ; Silverman, Daniel H S ; Parker, Elizabeth ; Grillo-López, Antonio J. / Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non-Hodgkin's lymphoma. In: Journal of Clinical Oncology. 1999 ; Vol. 17, No. 12. pp. 3793-3803.
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abstract = "Purpose: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy. Patients and Methods: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20+ B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59{\%} had at least one mass ≥ 5 cm. Results: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/μL). The overall response rate for the intent-to-treat population (n = 51) was 67{\%} (26{\%} complete response [CR]; 41{\%} partial response [PR]); for low-grade disease (n = 34), 82{\%} (26{\%} CR; 56{\%} PR); for intermediate-grade disease (n = 14), 43{\%}; and for mantle-cell disease (n = 3), 0{\%}. Responses occurred in patients with bulky disease (≥ 7 cm; 41{\%}) and splenomegaly (50{\%}). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2{\%}) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody). Conclusion: These phase I/II data demonstrate that IDEC-Y2B8 rodioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.",
author = "Witzig, {Thomas Elmer} and White, {Christine A.} and Wiseman, {Gregory A.} and Gordon, {Leo I.} and Christos Emmanouilides and Andrew Raubitschek and Nalini Janakiraman and John Gutheil and Schilder, {Russell J.} and Stewart Spies and Silverman, {Daniel H S} and Elizabeth Parker and Grillo-L{\'o}pez, {Antonio J.}",
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T1 - Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non-Hodgkin's lymphoma

AU - Witzig, Thomas Elmer

AU - White, Christine A.

AU - Wiseman, Gregory A.

AU - Gordon, Leo I.

AU - Emmanouilides, Christos

AU - Raubitschek, Andrew

AU - Janakiraman, Nalini

AU - Gutheil, John

AU - Schilder, Russell J.

AU - Spies, Stewart

AU - Silverman, Daniel H S

AU - Parker, Elizabeth

AU - Grillo-López, Antonio J.

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N2 - Purpose: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy. Patients and Methods: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20+ B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass ≥ 5 cm. Results: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/μL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (≥ 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2%) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody). Conclusion: These phase I/II data demonstrate that IDEC-Y2B8 rodioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.

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