Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies

Robert J. Kreitman, David R. Squires, Maryalice Stetler-Stevenson, Pierre Noel, David J P FitzGerald, Wyndham H. Wilson, Ira Pastan

Research output: Contribution to journalArticle

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Abstract

Purpose: To conduct a phase I trial of recombinant immunotoxin BL22, an anti-CD22 Fv fragment fused to truncated Pseudomonas exotoxin. Patients and Methods: Forty-six pretreated patients with CD22+ non-Hodgkin's lymphoma (NHL; n = 4), chronic lymphocytic leukemia (CLL; n = 11), and hairy cell leukemia (HCL; n = 31) received 265 cycles at 3 to 50 μg/Kg every other day × 3 doses. Results: BL22 was active in HCL, with 19 complete remissions (CRs; 61%) and six partial responses (PRs; 19%) in 31 patients. Of 19 CRs, 11 were achieved after one cycle and eight after two to 14 cycles. All 25 responders benefited clinically with one cycle. The CR rate was 86% in patients enrolled at > 40 μg/Kg every other day × 3, and 41% at lower doses (P = .011). The median duration for CR was 36 months (range, 5 to 66 months), and eight patients remain in CR at 45 months (range, 29 to 66 months). Lower but significant activity occurred in CLL. Neutralizing antibodies occurred in 11 (24%) of 46 patients (all HCL). A reversible hemolytic uremic syndrome requiring plasmapheresis was observed in one patient with NHL during cycle 1 and in four patients with HCL during cycle 2 or 3. The maximum-tolerated dose (MTD) evaluated at cycle 1 was 40 μg/Kg IV. QOD × 3. The most common toxicities at 30 to 50 μg/Kg every other day × 3 included hypoalbuminemia, transaminase elevations, fatigue, and edema. Conclusion: BL22 was well tolerated and highly effective in HCL, even after one cycle. Phase II testing is underway to define the efficacy with one cycle and to study safety when additional cycles are needed for optimal response.

Original languageEnglish (US)
Pages (from-to)6719-6729
Number of pages11
JournalJournal of Clinical Oncology
Volume23
Issue number27
DOIs
StatePublished - Sep 20 2005
Externally publishedYes

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B-Lymphocytes
Neoplasms
Immunoglobulin Variable Region
Hairy Cell Leukemia
Exotoxins
Hypoalbuminemia
Hemolytic-Uremic Syndrome
Plasmapheresis
Maximum Tolerated Dose
RFB4(dsFv)-PE38 recombinant immunotoxin
B-Cell Chronic Lymphocytic Leukemia
Pseudomonas
Transaminases
Neutralizing Antibodies
Non-Hodgkin's Lymphoma
Fatigue
Edema
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kreitman, R. J., Squires, D. R., Stetler-Stevenson, M., Noel, P., FitzGerald, D. J. P., Wilson, W. H., & Pastan, I. (2005). Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. Journal of Clinical Oncology, 23(27), 6719-6729. https://doi.org/10.1200/JCO.2005.11.437

Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. / Kreitman, Robert J.; Squires, David R.; Stetler-Stevenson, Maryalice; Noel, Pierre; FitzGerald, David J P; Wilson, Wyndham H.; Pastan, Ira.

In: Journal of Clinical Oncology, Vol. 23, No. 27, 20.09.2005, p. 6719-6729.

Research output: Contribution to journalArticle

Kreitman, RJ, Squires, DR, Stetler-Stevenson, M, Noel, P, FitzGerald, DJP, Wilson, WH & Pastan, I 2005, 'Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies', Journal of Clinical Oncology, vol. 23, no. 27, pp. 6719-6729. https://doi.org/10.1200/JCO.2005.11.437
Kreitman RJ, Squires DR, Stetler-Stevenson M, Noel P, FitzGerald DJP, Wilson WH et al. Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. Journal of Clinical Oncology. 2005 Sep 20;23(27):6719-6729. https://doi.org/10.1200/JCO.2005.11.437
Kreitman, Robert J. ; Squires, David R. ; Stetler-Stevenson, Maryalice ; Noel, Pierre ; FitzGerald, David J P ; Wilson, Wyndham H. ; Pastan, Ira. / Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 27. pp. 6719-6729.
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abstract = "Purpose: To conduct a phase I trial of recombinant immunotoxin BL22, an anti-CD22 Fv fragment fused to truncated Pseudomonas exotoxin. Patients and Methods: Forty-six pretreated patients with CD22+ non-Hodgkin's lymphoma (NHL; n = 4), chronic lymphocytic leukemia (CLL; n = 11), and hairy cell leukemia (HCL; n = 31) received 265 cycles at 3 to 50 μg/Kg every other day × 3 doses. Results: BL22 was active in HCL, with 19 complete remissions (CRs; 61{\%}) and six partial responses (PRs; 19{\%}) in 31 patients. Of 19 CRs, 11 were achieved after one cycle and eight after two to 14 cycles. All 25 responders benefited clinically with one cycle. The CR rate was 86{\%} in patients enrolled at > 40 μg/Kg every other day × 3, and 41{\%} at lower doses (P = .011). The median duration for CR was 36 months (range, 5 to 66 months), and eight patients remain in CR at 45 months (range, 29 to 66 months). Lower but significant activity occurred in CLL. Neutralizing antibodies occurred in 11 (24{\%}) of 46 patients (all HCL). A reversible hemolytic uremic syndrome requiring plasmapheresis was observed in one patient with NHL during cycle 1 and in four patients with HCL during cycle 2 or 3. The maximum-tolerated dose (MTD) evaluated at cycle 1 was 40 μg/Kg IV. QOD × 3. The most common toxicities at 30 to 50 μg/Kg every other day × 3 included hypoalbuminemia, transaminase elevations, fatigue, and edema. Conclusion: BL22 was well tolerated and highly effective in HCL, even after one cycle. Phase II testing is underway to define the efficacy with one cycle and to study safety when additional cycles are needed for optimal response.",
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