Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma

C. F. LeMaistre, S. Rosen, A. Frankel, S. Kornfeld, E. Saria, C. Meneghetti, J. Drajesk, D. Fishwild, P. Scannon, V. Byers

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Abstract

H65-RTA is an immunoconjugate that consists of the A chain of ricin (RTA), a ribosomal-inhibiting protein, coupled to a murine monoclonal antibody (H65) directed against the panT-cell antigen CDS. The CDS antigen is heterogeneously expressed on cutaneous T-cell lymphoma tumor cells, but is not expressed on normal cells except lymphocytes. A phase I trial was therefore conducted in which 14 patients with cutaneous T-cell lymphoma progressive on other therapies were treated with up to three cycles of H65-RTA. The maximal tolerated dose (MTD) of H65-RTA was 0.33 mg/kg/d administered intravenously for 10 days as defined by dyspnea at rest at higher doses. Other reversible side effects included myalgia, mild hypoalbuminemia with weight gain, pedal edema, fatigue, fevers, and chills. Six patients received more than one cycle of H65-RTA without increased side effects compared with the first cycle. Pharmacokinetic analysis showed that peak serum drug levels were dose-dependent, and ranged from 1.13 to 5.56 μg/mL, with a terminal half-life ranging from 1.0 to 2.9 hours. The development of antibodies against the immunoconjugate was associated with a lower peak drug level, but not with enhanced side effects. Partial responses lasting from 3 to 8 months were documented in four patients. Three of the responding patients received more than one cycle of H65-RTA in the presence of anti-immunoconjugate antibodies. The results from this phase I trial suggest that H65-RTA is an active drug in the treatment of cutaneous T-cell lymphoma. The immunoconjugate may be safely administered repeatedly, even in the presence of anti-immunoconjugate antibodies, with responses noted. Additional studies at the MTDare needed to define the response rate in this disease.

Original languageEnglish (US)
Pages (from-to)1173-1182
Number of pages10
JournalBlood
Volume78
Issue number5
StatePublished - Sep 1 1991

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Immunoconjugates
Cutaneous T-Cell Lymphoma
T-cells
Antibodies
Anti-Idiotypic Antibodies
Pharmaceutical Preparations
Ricin
Antigens
Hypoalbuminemia
Chills
Pharmacokinetics
Maximum Tolerated Dose
Lymphocytes
Rapid thermal annealing
Ribosomal Proteins
Myalgia
Dyspnea
Weight Gain
Antibody Formation
Fatigue

ASJC Scopus subject areas

  • Hematology

Cite this

LeMaistre, C. F., Rosen, S., Frankel, A., Kornfeld, S., Saria, E., Meneghetti, C., ... Byers, V. (1991). Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma. Blood, 78(5), 1173-1182.

Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma. / LeMaistre, C. F.; Rosen, S.; Frankel, A.; Kornfeld, S.; Saria, E.; Meneghetti, C.; Drajesk, J.; Fishwild, D.; Scannon, P.; Byers, V.

In: Blood, Vol. 78, No. 5, 01.09.1991, p. 1173-1182.

Research output: Contribution to journalArticle

LeMaistre, CF, Rosen, S, Frankel, A, Kornfeld, S, Saria, E, Meneghetti, C, Drajesk, J, Fishwild, D, Scannon, P & Byers, V 1991, 'Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma', Blood, vol. 78, no. 5, pp. 1173-1182.
LeMaistre CF, Rosen S, Frankel A, Kornfeld S, Saria E, Meneghetti C et al. Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma. Blood. 1991 Sep 1;78(5):1173-1182.
LeMaistre, C. F. ; Rosen, S. ; Frankel, A. ; Kornfeld, S. ; Saria, E. ; Meneghetti, C. ; Drajesk, J. ; Fishwild, D. ; Scannon, P. ; Byers, V. / Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma. In: Blood. 1991 ; Vol. 78, No. 5. pp. 1173-1182.
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AU - Saria, E.

AU - Meneghetti, C.

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N2 - H65-RTA is an immunoconjugate that consists of the A chain of ricin (RTA), a ribosomal-inhibiting protein, coupled to a murine monoclonal antibody (H65) directed against the panT-cell antigen CDS. The CDS antigen is heterogeneously expressed on cutaneous T-cell lymphoma tumor cells, but is not expressed on normal cells except lymphocytes. A phase I trial was therefore conducted in which 14 patients with cutaneous T-cell lymphoma progressive on other therapies were treated with up to three cycles of H65-RTA. The maximal tolerated dose (MTD) of H65-RTA was 0.33 mg/kg/d administered intravenously for 10 days as defined by dyspnea at rest at higher doses. Other reversible side effects included myalgia, mild hypoalbuminemia with weight gain, pedal edema, fatigue, fevers, and chills. Six patients received more than one cycle of H65-RTA without increased side effects compared with the first cycle. Pharmacokinetic analysis showed that peak serum drug levels were dose-dependent, and ranged from 1.13 to 5.56 μg/mL, with a terminal half-life ranging from 1.0 to 2.9 hours. The development of antibodies against the immunoconjugate was associated with a lower peak drug level, but not with enhanced side effects. Partial responses lasting from 3 to 8 months were documented in four patients. Three of the responding patients received more than one cycle of H65-RTA in the presence of anti-immunoconjugate antibodies. The results from this phase I trial suggest that H65-RTA is an active drug in the treatment of cutaneous T-cell lymphoma. The immunoconjugate may be safely administered repeatedly, even in the presence of anti-immunoconjugate antibodies, with responses noted. Additional studies at the MTDare needed to define the response rate in this disease.

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