A Multicenter Phase II Study Using a Dose Intensified Pediatric Regimen in Adults with Untreated Acute Lymphoblastic Leukemia. Session Type: Oral Session
Daniel J. DeAngelo, Suzanne Dahlberg, Lewis B. Silverman, Stephen Couban, Philip C. Amrein, Matthew D. Seftel, A. Robert Turner, Brian Leber, Kang Howsan-Jan, Martha Wadleigh, L. Andres Sirulnik, Jeffrey Supko, Ilene Galinsky, Stephen E. Sallan, Richard M. Stone Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; National Cancer Institute of Canada Clinical Trials Group, Kingston, ON, Canada; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada; Massachusetts General Hospital, Boston, MA, USA; Cancer Care Manitoba, Winnipeg, MB, Canada; Cross Cancer Institute, Edmonton, AB, Canada; Hamilton Health Sciences Centre, Hamilton, ON, Canada; London Health Sciences Services, London, ON, Canada
Background: Current chemotherapy regimens in children with ALL produce event-free survival (EFS) rates of greater than 80%. In contrast, adults with ALL have a much poorer prognosis, with EFS rates of 30-40%. Recent retrospective studies suggest that young adults may have superior outcomes when treated with intensive pediatric regimens. Unfortunately, prospective studies are lacking. This phase II trial was performed to determine if an intensive pediatric regimen could be administered to adults with ALL. Methods: The therapeutic backbone of this protocol is based on the high-risk arm of the DFCI Childhood ALL Consortium Protocol 00-01. Patients with newly diagnosed ALL received induction chemotherapy, which included doxorubicin, prednisone, vincristine, high-dose methotrexate, L-asparaginase (L-asp), and triple intrathecal therapy. CNS prophylaxis included triple intrathecal therapy and cranial radiation. Intensification therapy consisted of ten 3-week courses of doxorubicin, vincristine, dexamethasone, 6-mercaptopurine and 30 weeks of L-asp that was dosed to maintain asparagine depletion, defined as an L-asp level between 0.1 and 0.14. Continuation therapy consisted of 3 week courses of vincristine, dexamethasone, methotrexate and 6-mercaptopurine for a total of 2 years from an established complete remission (CR). Results: 89 patients have been enrolled and treated to date. The first 75 eligible patients were used for this analysis, 73 of whom had on-study data. Although there was no initial upper age restriction, the protocol was amended to include only patients between the ages of 18-50 with de novo ALL, which excluded 4 patients from the analysis. The median age was 28 years, (range, 18-50), 60% were male, 74% had B-lineage phenotype, and 20% were Philadelphia chromosome positive. The CR rate after 4 weeks was 84%. 39 patients had the opportunity to complete L-asp intensification therapy, and 27 (69%) completed all 30 weeks. The median L-asp dose was 16,582 U/m2 (starting dose was 12,500 U/m2). One death occurred during induction therapy (sepsis). Nine patients developed pancreatitis, one of whom died. This last case represented the only remission death on study. Two patients developed osteonecrosis, 14 thrombosis/embolism and 23 neutropenic infection during the post-remission period. With a median follow-up time of 15.3 months, the estimated 2-yr EFS is 72.5% (95%CI: 61-84%) and the estimated 2-yr overall survival (OS) is 77.1% (95%CI: 67-95%). Conclusions: The administration of a dose intensified pediatric regimen to adults with ALL is feasible. Although the high EFS and OS rates require longer follow up, such intensive treatment strategies for young adults with ALL could represent a major therapeutic advance.
Abstract #587 appears in Blood, Volume 110, issue 11, November 16, 2007
Disclosure: Research Funding: Enzon has partially funded the laboratory performing ASP enzyme level testing. Membership Information: Drs. DeAngelo and Stone have received honoraria for speaking engagements from Novartis, and Dr. DeAngelo has also received honoraria for speaking engagements from Pharmion, Celgene and Enzon. Dr. Stone has acted as a consultant for BMS and Genzyme. Dr. Sallan has acted as a consultant for OPi Pharmaceuticals.
Monday, December 10, 2007 4:30 PM
Session Info: Simultaneous Session: Acute Lymphocytic Leukemias: Pediatric and Adult Clinical Trials (3:30 p.m.-5:00 p.m.)