Preliminary Results of Phase II Trial of Clofarabine with Parenteral Busulfan Followed by Allogeneic Related or Unrelated Donor Transplantation for the Treatment of Hematologic Malignancies and Diseases.

Background: Nonablative transplant regimens are useful to treat patients who are elderly or too ill to undergo a full-intensity ablative allogeneic transplant regimen. However, this approach is limited by a higher relapse rate in some situations. We developed a novel conditioning regimen using the nucleoside analogue clofarabine (CLO) with busulfan (BU) to treat elderly patients with acute leukemia or high risk MDS who are not in remission or are at high risk of relapse.

Methods: Five patients were enrolled on this single institution; phase II, IRB-approved trial, so far. The diagnoses at the time of transplant were two with AML, one with ALL, and two with MDS. All patients received CLO 40mg/m²/day iv on d-7 through d-4 followed by BU 3.2 mg/m²/day iv on d-3 and -2, followed by infusion of HLA matched related or unrelated donor PBSC on day 0. GVHD prophylaxis consisted of oral FK506 and MTX 5mg/m² iv d + 1, +3 and +6. BU and CLO pharmacokinetic samples were collected on all patients for later PK analysis.

Results: Primary endpoints included toxicity and response to therapy. There were no cases of hepatic, cardiac, or renal toxicity attributed to the conditioning regimen by d+30. Acute toxicities included hand/foot syndrome, n=2 (one grade 1, and one grade 3 by CTCAE v 3.0); fluid retention, n=3 (2 grade 1 and 1 grade 2). All patients had hematologic nadirs lasting 12 to 15 days. GCSF was used in 4 of 5 subjects. 5 of 5 patients achieved allogeneic engraftment with myeloid cells by day +30. Response to therapy was documented in 4 patients by d+30, one is not yet evaluated. One (1) patient relapsed by d+62. 3 of 4 remain in remission with follow up ranging from 60 to 117 days.

Conclusions: CLO + BU is a novel allogeneic conditioning regimen that seems to be well tolerated by the small number of subjects treated so far at our institution. The follow up is not long enough to conclude more at this time. The study continues to accrue patients and will be updated at the meeting.