Phase I clinical study of atacicept in patients with relapsed and refractory B-cell non-Hodgkin's lymphoma

Stephen Maxted Ansell, Thomas Elmer Witzig, David J. Inwards, Luis F. Porrata, Arnaud Ythier, Lee Ferrande, Ivan Nestorov, Todd DeVries, Stacey R. Dillon, Diana Hausman, Anne J Novak

Research output: Contribution to journalArticle

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Abstract

Purpose: B-lymphocyte stimulator and a proliferation-inducing ligand regulate B-cell homeostasis and immunoglobulin production and are overexpressed in B-cell malignancies. Atacicept (TACI-Ig), a recombinant fusion protein that inhibits both B-lymphocyte stimulator and a proliferation-inducing ligand, may be a novel treatment for B-cell malignancies. Experimental Design: A phase 1, open-label, dose-escalation study of atacicept in patients with relapsed or refractory B-cell lymphoma was done. Atacicept was given s.c. weekly for 5 weeks to sequential patient cohorts at doses of 2, 4,7, or10 mg/kg. Patients responding or with stable disease were eligible for treatment on an extension study for up to 24 weeks or until disease progression. Results: All patients were heavily pretreated (median number of previous treatments, 5; range, 1-10), and four patients had previously received a stem cell transplant. Four patients were treated at the 2, 4, or 7 mg/kg dose levels, and three patients received 10 mg/kg of atacicept. Atacicept was well tolerated at all doses. Three adverse events with grade 3 severity were reported for one patient, including jaw pain, gastrointestinal hemorrhage, and sepsis; all were considered unrelated to atacicept. Pharmacokinetic results were nonlinear, and treatment with atacicept resulted in dose-dependent decreases in immunoglobulin concentrations. Two patients had stable disease at 8 weeks, entered the extension study, and received additional doses of atacicept with no safety or tolerability concerns. Conclusion: Atacicept at doses of up to 10 mg/kg was well tolerated and showed biological activity by decreasing immunoglobulin concentrations, although tumor responses were not observed.

Original languageEnglish (US)
Pages (from-to)1105-1110
Number of pages6
JournalClinical Cancer Research
Volume14
Issue number4
DOIs
StatePublished - Feb 15 2008

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B-Cell Lymphoma
Non-Hodgkin's Lymphoma
B-Cell Activating Factor
Immunoglobulins
B-Lymphocytes
Clinical Studies
TACI receptor-IgG Fc fragment fusion protein
Recombinant Fusion Proteins
Ligands
Neoplasms
Gastrointestinal Hemorrhage
Therapeutics
Jaw
Disease Progression
Sepsis
Homeostasis
Research Design
Stem Cells
Pharmacokinetics
Transplants

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I clinical study of atacicept in patients with relapsed and refractory B-cell non-Hodgkin's lymphoma. / Ansell, Stephen Maxted; Witzig, Thomas Elmer; Inwards, David J.; Porrata, Luis F.; Ythier, Arnaud; Ferrande, Lee; Nestorov, Ivan; DeVries, Todd; Dillon, Stacey R.; Hausman, Diana; Novak, Anne J.

In: Clinical Cancer Research, Vol. 14, No. 4, 15.02.2008, p. 1105-1110.

Research output: Contribution to journalArticle

Ansell, SM, Witzig, TE, Inwards, DJ, Porrata, LF, Ythier, A, Ferrande, L, Nestorov, I, DeVries, T, Dillon, SR, Hausman, D & Novak, AJ 2008, 'Phase I clinical study of atacicept in patients with relapsed and refractory B-cell non-Hodgkin's lymphoma', Clinical Cancer Research, vol. 14, no. 4, pp. 1105-1110. https://doi.org/10.1158/1078-0432.CCR-07-4435
Ansell, Stephen Maxted ; Witzig, Thomas Elmer ; Inwards, David J. ; Porrata, Luis F. ; Ythier, Arnaud ; Ferrande, Lee ; Nestorov, Ivan ; DeVries, Todd ; Dillon, Stacey R. ; Hausman, Diana ; Novak, Anne J. / Phase I clinical study of atacicept in patients with relapsed and refractory B-cell non-Hodgkin's lymphoma. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 4. pp. 1105-1110.
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AU - Ansell, Stephen Maxted

AU - Witzig, Thomas Elmer

AU - Inwards, David J.

AU - Porrata, Luis F.

AU - Ythier, Arnaud

AU - Ferrande, Lee

AU - Nestorov, Ivan

AU - DeVries, Todd

AU - Dillon, Stacey R.

AU - Hausman, Diana

AU - Novak, Anne J

PY - 2008/2/15

Y1 - 2008/2/15

N2 - Purpose: B-lymphocyte stimulator and a proliferation-inducing ligand regulate B-cell homeostasis and immunoglobulin production and are overexpressed in B-cell malignancies. Atacicept (TACI-Ig), a recombinant fusion protein that inhibits both B-lymphocyte stimulator and a proliferation-inducing ligand, may be a novel treatment for B-cell malignancies. Experimental Design: A phase 1, open-label, dose-escalation study of atacicept in patients with relapsed or refractory B-cell lymphoma was done. Atacicept was given s.c. weekly for 5 weeks to sequential patient cohorts at doses of 2, 4,7, or10 mg/kg. Patients responding or with stable disease were eligible for treatment on an extension study for up to 24 weeks or until disease progression. Results: All patients were heavily pretreated (median number of previous treatments, 5; range, 1-10), and four patients had previously received a stem cell transplant. Four patients were treated at the 2, 4, or 7 mg/kg dose levels, and three patients received 10 mg/kg of atacicept. Atacicept was well tolerated at all doses. Three adverse events with grade 3 severity were reported for one patient, including jaw pain, gastrointestinal hemorrhage, and sepsis; all were considered unrelated to atacicept. Pharmacokinetic results were nonlinear, and treatment with atacicept resulted in dose-dependent decreases in immunoglobulin concentrations. Two patients had stable disease at 8 weeks, entered the extension study, and received additional doses of atacicept with no safety or tolerability concerns. Conclusion: Atacicept at doses of up to 10 mg/kg was well tolerated and showed biological activity by decreasing immunoglobulin concentrations, although tumor responses were not observed.

AB - Purpose: B-lymphocyte stimulator and a proliferation-inducing ligand regulate B-cell homeostasis and immunoglobulin production and are overexpressed in B-cell malignancies. Atacicept (TACI-Ig), a recombinant fusion protein that inhibits both B-lymphocyte stimulator and a proliferation-inducing ligand, may be a novel treatment for B-cell malignancies. Experimental Design: A phase 1, open-label, dose-escalation study of atacicept in patients with relapsed or refractory B-cell lymphoma was done. Atacicept was given s.c. weekly for 5 weeks to sequential patient cohorts at doses of 2, 4,7, or10 mg/kg. Patients responding or with stable disease were eligible for treatment on an extension study for up to 24 weeks or until disease progression. Results: All patients were heavily pretreated (median number of previous treatments, 5; range, 1-10), and four patients had previously received a stem cell transplant. Four patients were treated at the 2, 4, or 7 mg/kg dose levels, and three patients received 10 mg/kg of atacicept. Atacicept was well tolerated at all doses. Three adverse events with grade 3 severity were reported for one patient, including jaw pain, gastrointestinal hemorrhage, and sepsis; all were considered unrelated to atacicept. Pharmacokinetic results were nonlinear, and treatment with atacicept resulted in dose-dependent decreases in immunoglobulin concentrations. Two patients had stable disease at 8 weeks, entered the extension study, and received additional doses of atacicept with no safety or tolerability concerns. Conclusion: Atacicept at doses of up to 10 mg/kg was well tolerated and showed biological activity by decreasing immunoglobulin concentrations, although tumor responses were not observed.

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