Another study of clofarabine in patients with relapsed or refractory lymphoma yielded similar results to Foss et al.5 The phase 1/2 study, which was conducted by Mulford et al, enrolled 29 patients with relapsed or refractory T or natural killer (NK)-cell lymphomas.

Overall, 17% of patients responded and 7 patients had disease stabilization. Again, activity was seen in patients with cutaneous T-cell lymphoma; there was no response in patients with B-cell disease. The MTD was identified at 28 mg/m2, with 1 patient experiencing pleural effusion and 1 patient experiencing prolonged thrombocytopenia.


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Based on these results, Foss and colleagues concluded that “clofarabine may be an active drug in T-cell lymphomas and could be further explored in patients who have not had extensive prior therapy.”

An oral formulation of clofarabine has, however, been tested in early clinical trials, though it failed to show activity in T-cell subtypes. A phase 1/2 trial evaluated oral clofarabine at 4 dose levels (1 mg, 2 mg, 3 mg, and 4 mg) in 50 patients with relapsed or refractory NHL of any subtype.6 Clofarabine was administered once daily on days 1 to 21 for a 28-day cycle.

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The overall response rate was 28%, with 10% of patients reaching a complete response and 36% of patients having stable disease. No responses were seen in patients with diffuse large B-cell lymphoma or T-cell lymphoma.

The most common toxicities were anemia, leukopenia, neutropenia, thrombocytopenia, and fatigue. Grade 3 to 4 leukopenia and neutropenia occurred in almost half of patients, and thrombocytopenia in one-third. 

References

  1. FDA approval for clofarabine. National Cancer Institute website. https://www.cancer.gov/about-cancer/treatment/drugs/fda-clofarabine. Updated July 2, 2013. Accessed February 2018.
  2. Jeha S, Gaynon PS, Razzouk BI, et al. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006;24(12):1917-23.
  3. Foss FM, Parker T. A phase I dose-escalation study of clofarabine in patients with relapsed or refractory low-grade or intermediate-grade B-cell or T-cell lymphoma. Oncologist. 2018 Feb 7. doi: 10.1634/theoncologist.2017-0658 [Epub ahead of print]
  4. Nabhan C, Davis N, Bitran JD et al. Efficacy and safety of clofarabine in relapsed and/or refractory non-Hodgkin lymphoma, including rituximab-refractory patients. Cancer. 2011;117:1490-7.
  5. Mulford DA, Pohlman BL, Hamlin PA et al. A phase I/II trial of clofarabine in patients with relapsed T-cell or NK-cell lymphomas. J Clin Oncol. 2010;28(suppl 15):8046A.
  6. Abramson JS, Jacobsen ED, Redd RA, et al. Oral clofarabine for relapsed/refractory non-Hodgkin lymphomas: final results from a phase 1-2 trial. Blood. 2014;124:4423.