Treating Multiply Relapsed or Refractory Hairy Cell Leukemia
Name of the Trial
Randomized Phase II Trial of Rituximab with Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia (NCI-10-C-0025). See the protocol summary.
Dr. Robert Kreitman, NCI Center for Cancer Research
Why This Trial Is Important
Hairy cell leukemia is an uncommon cancer of the blood in which the body produces a large number of abnormal B lymphocytes (a type of white blood cell). These abnormal cells appear “hairy” when viewed under a microscope and give the disease its name. Hairy cell leukemia is usually treated with a chemotherapy drug called cladribine when signs or symptoms of the disease develop, such as low blood cell counts, recurrent infections, or a swollen spleen.
Pentostatin, another chemotherapy drug in the same class as cladribine, is also effective against this cancer. However, most patients and doctors prefer cladribine because the typical course of treatment lasts 5–7 days as opposed to 3–6 months or longer with pentostatin. Cladribine and pentostatin have different mechanisms of action, but they both produce high rates of complete remission and have similar toxicity. Although responses to cladribine and pentostatin can last years or even decades, these drugs do not appear to cure most patients. Consequently, many patients relapse, need more treatment, and eventually develop resistant, or refractory, disease. Therefore, doctors are interested in finding new treatments or new combinations of existing treatments for patients with hairy cell leukemia who have relapsed or not responded to previous therapies.
A biological agent called rituximab binds to and kills cells that express an antigen called CD20 (CD20-positive cells). Moreover, rituximab has been used successfully to treat some patients with hairy cell leukemia who have relapsed or not responded to previous chemotherapy. Although the hairy cells that remain after cladribine or pentostatin treatment are essentially always CD20 positive, only a minority of patients respond to rituximab therapy alone. However, combinations of rituximab and either cladribine or pentostatin seem to be highly effective in nearly all patients. Dr. Kreitman is currently directing a randomized clinical trial of rituximab with cladribine in newly diagnosed (untreated) patients and patients who have had only one prior course of cladribine, but no prospective trial has yet evaluated rituximab with pentostatin in patients with hairy cell leukemia.
Yet another drug, called bendamustine, has been shown to be effective against other cancers involving B lymphocytes, such as some B-cell non-Hodgkin lymphomas and chronic lymphocytic leukemia. Bendamustine’s mechanism of action is different from those of cladribine and pentostatin, and it is known to act synergistically with rituximab in lymphoma cells. NCI researchers think that combining bendamustine and rituximab may prove effective in treating patients with multiply relapsed or refractory hairy cell leukemia.
In this trial, patients with hairy cell leukemia who have not responded to initial chemotherapy followed by second-line treatment with rituximab, or who have relapsed following two courses of chemotherapy, will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine. Either way, patients will be able to “crossover” to the other regimen if the first one does not work. Doctors will assess the objective response rates of each regimen and try to determine whether one regimen is superior.
“Most of the calls we get at NCI are from multiply relapsed hairy cell patients,” said Dr. Kreitman. “The majority of these patients will have received only cladribine, but because pentostatin works differently, some patients with disease that is refractory to cladribine may be sensitive to pentostatin. So it makes sense to use rituximab along with pentostatin as a comparator to bendamustine and rituximab for patients with multiply relapsed or refractory disease.”