Name of the Trial Cladribine with Simultaneous or Delayed Rituximab to Treat Hairy Cell Leukemia (NCI-09-C-0005). See the protocol summary .
Dr. Robert Kreitman
Principal Investigator Dr. Robert Kreitman, NCI Center for Cancer Research
Why This Trial Is Important Hairy cell leukemia is a rare type of cancer in which the body produces a large number of abnormal B lymphocytes . These lymphocytes appear “hairy” when viewed under a microscope and can be found in the bone marrow , spleen , and blood. Although hairy cell leukemia usually grows slowly, it does require treatment if symptoms and signs develop, such as low blood cell counts, recurrent infections, or a swollen spleen. Initial treatment with the chemotherapy drug cladribine usually induces a remission . However, there’s no evidence that, with remission, the disease is cured. Given time, it appears that all patients will relapse unless they die from something else first.
“If you follow patients over time (now about 20 years since the introduction of cladribine), you don’t find a plateau in the disease-free survival curve, which means that over time patients are still relapsing at a constant rate,” said Dr. Kreitman. “So eventually the disease will come back, at least for most, and, for younger patients in particular, this is a significant problem.”
Minimal residual disease can be found in a very high percentage of patients. The residual hairy cells often display an unusually high number of CD20 proteins. CD20 is an antigen found on the surface of all B lymphocytes, but the antigen is typically overexpressed in B-cell cancers like hairy cell leukemia. Consequently, CD20 is an important target for the treatment of these cancers. A monoclonal antibody called rituximab targets CD20 and has helped improve responses and survival in patients with several different types of B-cell diseases. Doctors want to see if the addition of rituximab to cladribine will eliminate minimal residual disease in patients with hairy cell leukemia.
In this trial, patients with hairy cell leukemia who have disease-related symptoms that require treatment, and who have not been treated or have had only one prior treatment with cladribine, will be randomly assigned to receive cladribine with either concurrent rituximab or rituximab at least 6 months after completing cladribine therapy. The primary endpoint of the study is to determine whether rituximab given at the same time as cladribine decreases minimal residual disease. Six months after initial treatment, patients given rituximab and cladribine together will be compared with those in the delayed-rituximab group to see if the rituximab is having a detectable effect.
“In terms of eradicating minimal residual disease long term, we don’t know whether it’s better to give rituximab at the same time as cladribine, or after 6 months,” said Dr. Kreitman. “Giving both agents concurrently may lead to a synergistic effect, with each agent enhancing the other. However, delaying rituximab until the cladribine has had time to eliminate most of the hairy cells may lead to a better possibility of eliminating disease altogether.
“It’s possible that patients receiving rituximab up front may fare better in the short term but that the delayed rituximab group will eventually catch up in terms of keeping the disease at bay,” he explained. “So both arms of the trial may end up producing equivalent outcomes, but those outcomes should be better than if the patients had received cladribine alone. Ultimately, we hope that eliminating minimal residual disease will lead to patients being cured or at least delaying any relapse until further into the future.”