Table 2 Complete clinical trials of CML therapies in combination with TKIs
From: Chronic myeloid leukemia stem cells: targeting therapeutic implications
Drug | Target to inhibit | Clinical phase | NCT number | Study population | Year | Purpose |
|---|---|---|---|---|---|---|
Imatinib + Dasatinib | BCR-ABL oncoprotein | Phase 2 | NCT00982488 | Patients with CML or Ph + ALL who treated with dasatinib or imatinib in previous protocols | 2009–2016 | Evaluate the long-term efficacy and tolerability of dasatinib |
 Imatinib + Dasatinib |  BCR-ABL oncoprotein |  Phase 2 | NCT00852566 | Patients with newly diagnosed CML | 2009–2015 | Compare the effect of treatment with dasatinib and imatinib on malignant stem cells at 18 months |
 Imatinib + Dasatinib |  BCR-ABL oncoprotein | Phase 3 | NCT00481247 | Patients with newly diagnosed CP-Ph + CML | 2007–2017 | compare the complete cytogenetic response and safety of treatment of dasatinib versus imatinib within 12 months |
Imatinib + Bosutinib | BCR-ABL oncoprotein | Phase 3 | NCT02130557 | Patients with newly diagnosed CML | 2014–2020 | Investigate the randomized receiving of bosutinib or imatinib and the use of bosutinib as first-line treatment for CML patients |
 Imatinib + Bosutinib |  BCR-ABL oncoprotein |  Phase 3 | NCT00574873 | Patients with newly diagnosed CP-CML | 2007–2019 | Compare the efficacy and safety of Bosutinib versus imatinib alone |
Imatinib + Nilotinib | BCR-ABL oncoprotein | Phase 2 | NCT00769327 | Patients with early CP-CML | 2009–2014 | Evaluate the efficacy of nilotinib together with imatinib in treatment |
 Imatinib + Nilotinib |  BCR-ABL oncoprotein | Phase 3 | NCT01275196 | Patients with newly diagnosed CP-CML | 2011–2016 | Compare the efficacy and safety of nilotinib versus imatinib alone |
 Imatinib + Nilotinib |  BCR-ABL oncoprotein |  Phase 3 | NCT02272777 | Patients with CP-CML after the end of CAMN107ECN02 study | 2014–2019 | The extension study followed the CAMN107ECN02 core study (NCT01275196) |
 Imatinib + Nilotinib |  BCR-ABL oncoprotein |  Phase 3 | NCT00760877 | Patients with CP-CML with evidence of persistent Leukemia | 2008–2016 | Compare the Kinetics of complete molecular response in subjects receiving imatinib or nilotinib therapy |
 Imatinib + Nilotinib |  BCR-ABL oncoprotein |  Phase 3 | NCT00802841 | Patients with CP-CML and suboptimal response to standard dose imatinib | 2008–2015 | Compare effectiveness of imatinib dose escalation (600 mg once daily) versus nilotinib (400 mg twice daily) in terms of complete cytogenetic response after 6 months |
 Imatinib + Nilotinib |  BCR-ABL oncoprotein |  Phase 3 | NCT00471497 | Patients with newly diagnosed CP-CML | 2013–2020 | Compare the efficacy and safety of nilotinib versus imatinib |
Imatinib + Dasatinib + Nilotinib | BCR-ABL oncoprotein | Phase 2 | NCT02709083 | Patients with newly diagnosed CP-CML and previously untreated | 2016–2018 | Assess the efficacy of treatment with first-line dasatinib or nilotinib followed by response guided switch to imatinib |
Imatinib + Recombinant Interferon-alpha (INF-α) | BCR-ABL oncoprotein + growth of leukemia cells | Phase 2 | NCT00015847 | Patients with CML | 2003–2011 | Investigate the efficacy of combining imatinib with INF-α in the treatment |
Imatinib + Interferon-alpha (INF-α) + Cytarabine (ARA-C) | BCR-ABL oncoprotein + growth of leukemia cells | Phase 3 | NCT00333840 | Patients With Newly Diagnosed Previously Untreated (Ph+) CP-CML | 2000–2012 | Evaluate and compare the side effects and antileukemic benefits of imatinib with those of IFN and ARA-C for patients |
Imatinib + Homoharringtonine | BCR-ABL oncoprotein + SMAD3 and TGF-β pathway | Phase 2 | NCT00114959 | Patients with CML in chronic, accelerated or blast phase who have developed resistance to or have failed previous treatment with Gleevec | 2005–2009 | Investigate the safety and efficacy of this combination therapy to produce a stronger hematologic or cytogenetic response for a period of 12 cycles in comparison with imatinib alone |
Nilotinib + Ruxolitinb | BCR-ABL oncoprotein + alternative pathway independent of BCR-ABL including JAK2/STAT5 | Phase 1 and 2 | NCT01914484 | Patients with Ph + CML and ALL who have are resistant to prior TKIs | 2013–2018 | Investigate the effectiveness of a nilotinib and ruxolitinib combination treatment |
|  |  | Phase 1 | NCT01702064 | Patients with CP-CML | 2013–2019 | Determine the maximum tolerated dosage of ruxolitinib as used with nilotinib for therapy |
Nilotinib + Sonidegib (LDE225) | BCR-ABL oncoprotein + SMO/Hedgehog signaling pathway | Phase 1 | NCT01456676 | Patients with CP/AP-CML | 2012–2014 | Determine the effectiveness of combination nilotinib and LDE225 in treatment |
Dasatinib (Sprycel) + Decitabine (Dacogen) | BCR-ABL oncoprotein + Nucleic acid synthesis and expression of certain genes | Phase 1 and 2 | NCT01498445 | Patients With Accelerated or Blastic Phase CML | 2012–2019 | Assess whether combining dasatinib and decitabine will potentially affect CML, as well as investigate the optimal dose of Decitabine |
Dasatinib (BMS-354825) + Nivolumab (BMS-936558) | BCR-ABL oncoprotein + PD-1 Blocking antibody | Phase1B | NCT02011945 | Patients with CML | 2013–2020 | Dose escalation study in patients with dasatinib and nivolumab to determine safety, tolerability, and preliminary efficacy |
Dasatinib + Smoothened (SMO) antagonist (BMS-833923) | BCR-ABL oncoprotein + SMO/Hedgehog signaling pathway | Phase 1 and 2 | NCT01218477 | Patients with CML | 2010–2016 | Determine the safety and tolerability result of the combination of BMS-833923 plus dasatinib in CML patients |
Dasatinib + Peginterferon-α-2b | BCR-ABL oncoprotein + inducer of immunosurveillance | Phase 2 | NCT01872442 | Patients With newly diagnosed CP-CML | 2013–2018 | Investigate the efficacy and safety of dasatinib in combination with low dose of Peg-IFNα-2b as frontline therapy |
Imatinib mesylate + panobinostat (LBH589) | BCR-ABL oncoprotein + Histone deacetyation activity | Phase 1 | NCT00686218 | Patients with previously treated CP-CML | 2008–2014 | Determine the efficacy and tolerability of Panobinostat combined with imatinib in the treatment of patients |
Tyrosine Kinase Inhibitor (TKI) + Pioglitazone (PIO) | BCR-ABL oncoprotein + A diabetic drug against kinase A or kinase B | Phase 2 | NCT02730195 | CML patients who relapsed Following a First TKI Discontinuation | 2016–2019 | Assess safety of these drug combination in CML subjects and their survival following a second TKI discontinuation |
Tyrosine Kinase Inhibitor (TKI) + Azacitidine (AZA) | BCR-ABL oncoprotein + Changes in genes that are thought to cause leukemia | Phase 1 | NCT01460498 | Patients With CML Who have Minimal Residual Disease while receiving TKI therapy | 2012–2019 | Consider the most effective and tolerable dose of Azacitidine that can be administered with a TKI to improve treatment |