Table 1.
Ongoing Clinical Trials for Reduced/Interrupted Dosing of Dasatinib
| Registry Information | Trial Title | Arm(s) (No. of Patients Enrolled) | Intervention(s) | Endpoints |
|---|---|---|---|---|
| UMIN000007345 (Japanese Ministry of Health; DARIA‐01 study)11, 33 | A Phase 2 Study Of Midterm Compliance And Effectiveness Of Dasatinib Therapy In Patients With CML | Single‐arm (N = 32) | Dasatinib at a dose of 100 mg/d, which was either interrupted or lowered to 50 mg/d |
• Compliance with dasatinib therapy at 12 mo • Treatment‐related toxicity • Relationship between serum concentration of dasatinib and clinical result • OS and PFS rates at 1 y |
| http://ClinicalTrials.gov identifier NCT01916785 (OPTIM DASATINIB)14, 34 | OPTIM DASATINIB (Optimized Tyrosine Kinase Inhibitors Monotherapy) | Two arms, randomized (N = 289) | Dasatinib doses will be optimized based on plasma values (target Cmin ≥3 nmol/L); dasatinib doses start at 100 mg/d |
• Cumulative rate of significant AEsa
• Rate and duration of treatment interruptions • Dose of dasatinib • Cumulative rates of CCyR, CMR, and MMR • Time to molecular response • Correlation between dasatinib plasma levels and efficacy • OS and PFS at 5 y • Lymphocyte counts before and during dasatinib • Rate of sustained major molecular remission after dasatinib discontinuation |
| UMIN000003499 (Japanese Ministry of Health)36 | Phase 2 Clinical Trial Of Low‐Dose Dasatinib In Patients With Resistant Or Intolerant CML Who Are Treated With Low‐Dose Imatinib | Single‐arm (N = 30)b | Dasatinib at a dose of 50 mg/d, then 100 mg/d | • MMR after 12 mo |
| ACTRN12616000738426 (Australia; CML12 DIRECT)55 | The DIRECT study: Individualized Dasatinib Dosing For Elderly Patients With Chronic Myelogenous Leukemia | Single‐arm (N = 80)b | Patients aged ≥60 y will receive dasatinib at a dose of 100 mg/d, 70 mg/d, 50 mg/d, or 50 mg every other d |
• Incidence of treatment‐related pleural effusion • Molecular responses • Survival • Correlation between dasatinib trough levels, intensity, and response and toxicity • QOL • Percentage of patients eligible for treatment‐free remission • Percentage of patients with different mechanisms of resistance • Overall tolerability |
| http://ClinicalTrials.gov identifier NCT01804985 (DESTINY)28 | De‐Escalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel in Chronic Myeloid Leukaemia | Three arms, open‐label (N = 168)b | Imatinib, nilotinib, or dasatinib, at one‐half the standard dose for 12 mo (imatinib, 200 mg/d; nilotinib, 400 mg/d; dasatinib, 50 mg/d) |
• Percentage of patients who maintain MMR on one‐half dose for 12 mo, then discontinue drug for 24 mo • Percentage of patients who regain MMR after reinitiating TKI • QOL • Health economic assessment • Investigation of patients more likely to develop disease recurrence through laboratory values |
| http://ClinicalTrials.gov identifier NCT0268944029 | Therapy of Early Chronic Phase CML With Dasatinib | Single‐arm (N = 100)b | Dasatinib at a dose of 50 mg/d |
• MMR at 12 mo • CCyR at 6 mo |
| LN_CMLSTU_2015_576 (European Leukemia Trial Registry; DasaHIT)30 | Treatment optimization for patients with CML with treatment‐naïve disease (first‐line) and patients with resistance or intolerance against alternative Abl‐Kinase inhibitors (≥second‐line) | Two arms, randomized (N = 306)b | NA |
• The cumulative toxicity score after 2 y of dasatinib treatment • MMR as assessed by BCR‐ABL1 (IS) monitoring by 24 mo |
| http://ClinicalTrials.gov identifier NCT0232631131 | Optimization of TKIs Treatment and Quality of Life in Ph+ CML Patients ≥60 Years in Deep Molecular Response | Two arms, randomized (N = 502)b | Fixed (1 mo on/1 mo off) vs progressive (1 mo on/1 mo off for the 1st y; 1 mo on/2 mo off for the 2nd y; 1 mo on/3 mo off for the 3rd y) intermittent administration of imatinib, dasatinib, or nilotinib | • Change in QOL from baseline, then at 3, 6, 12, 18, 24, 30, and 36 mo |
| http://ClinicalTrials.gov identifier NCT02348957 (DasPAQT)32 | Treating Patients With CML in Chronic Phase With Dasatinib | Observational (N = 300)b | This study is designed to collect real‐life data regarding CML treatment with dasatinib, with respect to first‐line and second‐line treatment, and switching from another TKI in first‐line to dasatinib in second‐line (it is anticipated that dose modifications will be part of the real‐life setting) |
• Distribution of molecular remission status at study entry and after 12 mo and 24 mo • Best possible response • Time to molecular remission and disease progression • Cytogenetic profile • Hematologic response • Patient adherence • Patient satisfaction • QOL • Safety and tolerability |
Abbreviations: AE, adverse event; Cmin, minimal plasma concentration; CCyR, complete cytogenetic response; CML, chronic myeloid leukemia; CMR, complete molecular response; IS, International Scale; MMR, major molecular response (BCR‐ABL1 [IS] < 0.1%); NA, not available; OS, overall survival; PFS, progression‐free survival; Ph+, Philadelphia chromosome positive; QOL, quality of life; TKI, tyrosine kinase inhibitor.
a
Defined by grade 3 to 4 fluid retention, all‐grade pleural effusion, hematological grade 3 to 4 AEs related to dasatinib, and/or all AEs leading to dasatinib discontinuation within the first year of therapy.
b
Estimated enrollment.