Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence ¹ for more information.)

Standard treatment options:

1. Imatinib mesylate has demonstrated marked activity in patients with myeloid blast crisis and in patients with lymphoid blast crisis or Philadelphia chromosome-positive acute lymphoblastic leukemia. In a phase I trial, 4 of 38 patients with myeloid blast crisis had a complete hematologic remission, and 17 patients had a decrease in blasts in the marrow to 15% or less.[1] Of the 20 patients in the lymphoid cohort, 4 patients had a complete hematologic response, and 10 patients had a decrease in blasts in the marrow to 15% or less. These kinds of responses have not been durable. Of 21 responding patients with myeloid blast crisis, 9 relapsed between 42 and 194 days; of the 14 responding patients with lymphoid disease, 12 relapsed with a median duration of time to relapse of 58 days. Seven of the 21 responding patients with myeloid blast crisis continue in remission with longest follow-up of 349 days. These response data are the highest single agent responses in this disease.[1]

   Two larger trials involving a total of 304 patients in blastic-phase chronic myelogenous leukemia (CML) confirm a hematologic response rate of 52% to 55% and a major cytogenetic response rate of 16%, but the estimated 1-year survival is under 35%.[2,3][Level of evidence: 3iiiA] Clinical trials will explore combining imatinib mesylate with other drugs to improve the prognosis of patients with blastic-phase CML.[4]

2. Vincristine and prednisone with or without an anthracycline (for the approximately 25% of patients with terminal deoxynucleotidyl transferase-positive cells and lymphoblastic transformation).[5,6]
3. Allogeneic bone marrow transplantation (BMT) is successful in less than 10% of patients because of complications of transplantation and recurrent leukemia.[7] If available, this represents the only potentially curative approach in such patients. Allogeneic BMT is more effective in patients induced into a second chronic phase, with long-term disease-free survival approximating 20%.[8]
4. Hydroxyurea as palliative therapy.
5. High-dose cytarabine.[9]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with blastic phase chronic myelogenous leukemia ². The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site ³.

References

1. Druker BJ, Sawyers CL, Kantarjian H, et al.: Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344 (14): 1038-42, 2001.  [PUBMED Abstract]
   
   
2. Kantarjian HM, Cortes J, O'Brien S, et al.: Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. Blood 99 (10): 3547-53, 2002.  [PUBMED Abstract]
   
   
3. Sawyers CL, Hochhaus A, Feldman E, et al.: Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 99 (10): 3530-9, 2002.  [PUBMED Abstract]
   
   
4. Fruehauf S, Topaly J, Buss EC, et al.: Imatinib combined with mitoxantrone/etoposide and cytarabine is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis. Cancer 109 (8): 1543-9, 2007.  [PUBMED Abstract]
   
   
5. Preti HA, O'Brien S, Giralt S, et al.: Philadelphia-chromosome-positive adult acute lymphocytic leukemia: characteristics, treatment results, and prognosis in 41 patients. Am J Med 97 (1): 60-5, 1994.  [PUBMED Abstract]
   
   
6. Walters RS, Kantarjian HM, Keating MJ, et al.: Therapy of lymphoid and undifferentiated chronic myelogenous leukemia in blast crisis with continuous vincristine and adriamycin infusions plus high-dose decadron. Cancer 60 (8): 1708-12, 1987.  [PUBMED Abstract]
   
   
7. Copelan EA, Grever MR, Kapoor N, et al.: Marrow transplantation following busulfan and cyclophosphamide for chronic myelogenous leukaemia in accelerated or blastic phase. Br J Haematol 71 (4): 487-91, 1989.  [PUBMED Abstract]
   
   
8. Gratwohl A, Hermans J, Niederwieser D, et al.: Bone marrow transplantation for chronic myeloid leukemia: long-term results. Chronic Leukemia Working Party of the European Group for Bone Marrow Transplantation. Bone Marrow Transplant 12 (5): 509-16, 1993.  [PUBMED Abstract]
   
   
9. Kantarjian HM, Talpaz M, Kontoyiannis D, et al.: Treatment of chronic myelogenous leukemia in accelerated and blastic phases with daunorubicin, high-dose cytarabine, and granulocyte-macrophage colony-stimulating factor. J Clin Oncol 10 (3): 398-405, 1992.  [PUBMED Abstract]
   
   

Glossary Terms

Nonconsecutive case series with total mortality as an endpoint. See Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (PDQ®) for more information.