A phase II multicenter study of troxacitabine in relapsed or refractory lymphoproliferative neoplasms or multiple myeloma

Julie Vose, Amit Panwalkar, Robert Belanger, Bertrand Coiffier, Michele Baccarani, Stephanie Gregory, Thierry Facon, Renato Fanin, Dolores Caballero, Dina Ben-Yehuda, Francis Giles

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Options for patients with relapsed/refractory lymphoproliferative disorders and multiple myeloma are currently limited. Troxacitabine has shown promise in preclinical studies in a variety of malignancies; hence, the current study was conducted to evaluate the activity of troxacitabine in relapsed or refractory lymphoid malignancies. This was a phase II, open-label, multinational, multicenter study of patients with relapsed or refractory lymphoproliferative disorders or multiple myeloma. Thirty-four adults were enrolled in the study and received the study drug at either 5.4 mg/m2 (n=16) or 4.3 mg/m2 (n=18). The dose was decided in a phase I study, during which dose escalation was carried to reach a maximum tolerated dose with an acceptable toxicity profile. Two separate phase I studies were performed in Europe and the US. Troxacitabine was administered by intravenous infusion over 30 min daily for days 1-5 every 4 weeks. Treatment was continued to disease progression or until the subjects met criteria for withdrawal or unacceptable toxicities were evident as outlined in the protocol. Two patients had a partial response (PR) to treatment with troxacitabine to yield an overall response rate of 13%. There were no complete responses seen with the drug. Stable disease was achieved in 15 patients (44%). All patients had at least one treatment related adverse event, which led to six withdrawals from the study. Hematologic toxicity constituted the most common adverse events. Serious adverse effects were seen in 62% of patients. None of the 13 deaths were attributed directly to troxacitabine. As a single agent, troxacitabine has limited benefit in patients with advanced lymphoproliferative disorders or multiple myeloma. Future studies will be needed to address modified dosing according to emerging pharmacokinetic and pharmacodynamic data and combination therapy which may lead to improved clinical benefit for troxacitabine in hematologic malignancies.

Original languageAmerican English
Pages (from-to)39-45
Number of pages7
JournalLeukemia and Lymphoma
Volume48
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Bibliographical note

Funding Information:
This was a phase II, open-label, multinational, multicenter study. Due to the difficulties of doing a phase I study in multiple countries, there were separate phase I studies in Europe and the USA. The phase II portion then started at each dose chosen by the phase I studies. Eleven centers in the USA, Canada, France, Israel, Italy and Spain participated (see Appendix). The primary objective of the study was to determine the recommended dose, and clinical activity of troxacitabine in patients with relapsed or refractory lymphoproliferative disorders or multiple myeloma. The secondary objective was to determine the toxicity profile, and time to disease progression following treatment with troxacitabine in patients with relapsed or refractory lymphoprolifera-tive disorders or multiple myeloma. The study was sponsored by Shire Pharmaceuticals Ltd. with monitoring by PPD Development Inc. and Pharma-Net CRO. Data management was performed by Quintiles Inc.

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