The MDS Beacon™

Oral Clolar (clofarabine) may be an effective treatment for people with higher-risk myelodysplastic syndromes (MDS), according to a Phase 2 clinical trial published recently in the Journal of Clinical Oncology. Out of 22 study participants who had higher-risk MDS, half responded to oral Clolar treatment.

The only use for Clolar approved by the Food and Drug Administration is for children with acute lymphoblastic leukemia that has relapsed or has not responded to treatment. However, recent research has focused on Clolar’s promise in MDS, as the Beacon reported previously.

“The development of oral clofarabine seemed ideal for patients with MDS,” wrote scientists in their Journal of Clinical Oncology article. Their research also addresses dosing and on which MDS patients might benefit most from Clolar.

The trial examined 32 people with MDS or chronic myelomonocytic leukemia, including 22 people with higher-risk MDS. Nine of the study participants had secondary MDS, and 20 had been unsuccessfully treated with the standard drugs Vidaza (azacitidine) or Dacogen (decitabine). The participants’ median age was 70.

Researchers treated the participants with oral Clolar for five days. This course of treatment was repeated every four to eight weeks for up to 12 courses. Depending on each participant’s response, the initial dose of 40 mg/m² was reduced to 30 mg/m² or 20 mg/m² in subsequent treatment cycles.

Five people with higher-risk MDS achieved a complete response, meeting certain standards in their cell counts for neutrophils, platelets, and marrow blasts. Three higher-risk MDS participants met these cell count markers for neutrophils and marrow blasts, but not platelets. An additional three higher-risk MDS participants saw platelet increases, neutrophils increases, or increases in their hemoglobin, the protein in the blood that carries oxygen. The median overall survival time for people with higher-risk MDS was eight months after the start of Clolar treatment.

Overall, 50 percent of people with higher-risk MDS responded to Clolar treatment. That number is less than the number of those who respond to Vidaza or Dacogen, which work for up to 60 percent of patients, researchers reported. However Clolar could be a valuable treatment because not everyone responds to those drugs, and because people relapse, the researchers added. In this study, six people who had previously been treated with Vidaza or Dacogen responded to Clolar, but their survival times were shorter than those who had not been treated.

The most common mild-to-moderate side effects of the Clolar treatment were nausea, vomiting, and rash. The most common severe side effects were kidney damage and, for four study participants, infections that led to acute kidney failure. Two of those with kidney failure died during the study, and the other two died after the study was over. Overall, three patients died during the study, all from complications of longtime low white blood cell counts and infection.

Because the lowest dose they studied, 20 mg/m², worked as well as higher doses, the researchers plan to check even lower doses in a future study, to help reduce side effects.

Clolar may emerge as a salvage therapy for those who do not respond to Vidaza or Dacogen, researchers concluded in their paper. They also suggested studying combining Clolar with known effective drugs as a front-line therapy for people with higher-risk MDS.

For more information, please see the study in the Journal of Clinical Oncology (abstract).