Current Clinical Trials

Overt failure is defined as a loss of hematologic remission or progression to accelerated phase or blast crisis phase as previously defined. Although presumed to represent relapsing disease, a rising quantitative reverse transcriptase–polymerase chain reaction signal is a controversial finding. Prospective studies comparing resumption of therapy versus continued observation have not been performed. Similarly, there has been no prospective validation for failure to achieve certain benchmarks during initial therapy. For initial use of imatinib mesylate, the designation of relative failure has been proposed for lack of complete hematologic remission by 3 months, no cytogenetic response by 6 months, or no major cytogenetic response by 12 months.[1]

Mutations in the tyrosine kinase domain can confer resistance to imatinib mesylate; alternative inhibitors such as dasatinib or nilotinib, higher doses of imatinib mesylate, and allogeneic stem cell transplantation (SCT) are being studied, as evidenced in the UCLA-0501047-01 trial, for example, in this setting.[2-11] Clinical trial participation should help establish the optimal sequence of these options.

Infusions of buffy coat leukocytes or isolated T cells obtained by pheresis from the bone marrow transplant donor have induced long-term remissions in more than 50% of patients who relapse following allogeneic transplant.[12,13] The efficacy of this treatment is thought to be the result of an immunologic graft-versus-leukemia effect. This treatment is most effective for patients whose relapse is detectable only by cytogenetics or molecular studies and is associated with significant graft-versus-host disease. After relapse from allogeneic SCT, some patients will also respond to interferon-alpha.[14] Most patients will respond to imatinib mesylate with durable (>1 year) cytogenetic and molecular responses. (These patients had not previously received imatinib.)[15-17]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with relapsing chronic myelogenous leukemia. 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.

References

1. Baccarani M, Saglio G, Goldman J, et al.: Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 108 (6): 1809-20, 2006.  [PUBMED Abstract]
   
   
2. Jabbour E, Cortes J, Kantarjian HM, et al.: Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure. Blood 108 (4): 1421-3, 2006.  [PUBMED Abstract]
   
   
3. le Coutre P, Ottmann OG, Giles F, et al.: Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood 111 (4): 1834-9, 2008.  [PUBMED Abstract]
   
   
4. Talpaz M, Shah NP, Kantarjian H, et al.: Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354 (24): 2531-41, 2006.  [PUBMED Abstract]
   
   
5. Hochhaus A, Baccarani M, Deininger M, et al.: Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia 22 (6): 1200-6, 2008.  [PUBMED Abstract]
   
   
6. Quintas-Cardama A, Kantarjian H, Jones D, et al.: Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure. Blood 109 (2): 497-9, 2007.  [PUBMED Abstract]
   
   
7. Cortes J, Rousselot P, Kim DW, et al.: Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood 109 (8): 3207-13, 2007.  [PUBMED Abstract]
   
   
8. Kantarjian H, Pasquini R, Hamerschlak N, et al.: Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood 109 (12): 5143-50, 2007.  [PUBMED Abstract]
   
   
9. Guilhot F, Apperley J, Kim DW, et al.: Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood 109 (10): 4143-50, 2007.  [PUBMED Abstract]
   
   
10. Kantarjian HM, Giles F, Gattermann N, et al.: Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood 110 (10): 3540-6, 2007.  [PUBMED Abstract]
    
    
11. Shah NP, Kantarjian HM, Kim DW, et al.: Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol 26 (19): 3204-12, 2008.  [PUBMED Abstract]
    
    
12. Kaeda J, O'Shea D, Szydlo RM, et al.: Serial measurement of BCR-ABL transcripts in the peripheral blood after allogeneic stem cell transplantation for chronic myeloid leukemia: an attempt to define patients who may not require further therapy. Blood 107 (10): 4171-6, 2006.  [PUBMED Abstract]
    
    
13. Dazzi F, Szydlo RM, Craddock C, et al.: Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood 95 (1): 67-71, 2000.  [PUBMED Abstract]
    
    
14. Pigneux A, Devergie A, Pochitaloff M, et al.: Recombinant alpha-interferon as treatment for chronic myelogenous leukemia in relapse after allogeneic bone marrow transplantation: a report from the Société Française de Greffe de Moelle. Bone Marrow Transplant 15 (6): 819-24, 1995.  [PUBMED Abstract]
    
    
15. Olavarria E, Ottmann OG, Deininger M, et al.: Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia 17 (9): 1707-12, 2003.  [PUBMED Abstract]
    
    
16. Kantarjian HM, O'Brien S, Cortes JE, et al.: Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 100 (5): 1590-5, 2002.  [PUBMED Abstract]
    
    
17. Hess G, Bunjes D, Siegert W, et al.: Sustained complete molecular remissions after treatment with imatinib-mesylate in patients with failure after allogeneic stem cell transplantation for chronic myelogenous leukemia: results of a prospective phase II open-label multicenter study. J Clin Oncol 23 (30): 7583-93, 2005.  [PUBMED Abstract]
    
    

Back to Top

< Previous Section  |  Next Section >