Key phase 3 randomized studies for Ph+ ALL
| Group/study/years . | TKI . | Randomization question . | N . | Age in years, median (range) . | CR (%) . | Early mortality (%) . | Molecular response (%) . | alloHCT, CR1 (%) . | RFS/EFS (%) . | OS (%) . |
|---|---|---|---|---|---|---|---|---|---|---|
| GRAALL(SAKK) GRAAPH-2005 NCT00327678 2006-2011 | IM | Induction intensity: low (vincristine, dex) vs high (hyper-CVAD) | 266 135 low (A) 133 high (B) | 47 (18-59) 45 (18-59) 45 (21-59) | 94.8 98.5 91.0 p = 0.006 | 5.6 (day 60) 2.2 9.0 p = 0.017 | 25.8 (MR4, C2) 28.6 22.6 p = 0.35 | 63.3 61.6 65.3 p = 0.53 | 37.1 (5-yr EFS) 42.2 (5-yr EFS) 32.1 (5-yr EFS) p = 0.13 | 45.6 (5 yr) 48.3 (5 yr) 43.0 (5 yr) p = 0.37 |
| GRAALL(SAKK) GRAAPH-2014 NCT02611492 2016-2019 | NIL | Consolidation intensity: low (HD-MTX) vs high (HiDAC, HD-MTX) | 156 79 low (B) 77 high (A) | 47 (IQR 39-54) 47 (IQR 39-54) 49 (IQR 39-54) | 94.2 94.9 93.4 p = 0.74 | 3.2 (day 60) 2.5 3.9 p = 0.68 | 26.4 (MR4, C4) 24.1 28.9 p = 0.59 | 60.0 59.5 60.5 p = 0.97 | - 58.5 (4-yr RFS) 76.2 (4-yr RFS) p = 0.029 | - 73.4 (4 yr) 79.4 (4 yr) p = 0.27 |
| China CCCG-ALL2015 ChiCTR-IPR-14005706 2015-2018 | IM vs DAS | IM vs DAS with chemo | 189 97 IM 92 DAS | 7.8 (IQR 5-11) - - | 96.8 94.8 98.9 p = 0.21 | 1 death (IM arm) | - | None | - 48.9 (4-yr EFS) 71.0 (4-yr EFS) p = 0.005 | - 69.2 (4-yr) 88.4 (4-yr) p = 0.04 |
| Global PhALLCON NCT03589326 2018-2022 | IM vs PON | IM vs PON with low-intensity chemo | 245 81 IM 163 PON | 54 (19-82) 52 (19-75) 54 (19-82) | - | 0 | (MR4, C9) 44.9 62.1 | 32.7 37.0 30.5 | - Med EFS 29 mos Med EFS NR (HR 0.65, 95% CI 0.39-1.1) | - Med OS NR Med OS NR (HR 0.76, 95% CI 0.38-1.5) |
| Group/study/years . | TKI . | Randomization question . | N . | Age in years, median (range) . | CR (%) . | Early mortality (%) . | Molecular response (%) . | alloHCT, CR1 (%) . | RFS/EFS (%) . | OS (%) . |
|---|---|---|---|---|---|---|---|---|---|---|
| GRAALL(SAKK) GRAAPH-2005 NCT00327678 2006-2011 | IM | Induction intensity: low (vincristine, dex) vs high (hyper-CVAD) | 266 135 low (A) 133 high (B) | 47 (18-59) 45 (18-59) 45 (21-59) | 94.8 98.5 91.0 p = 0.006 | 5.6 (day 60) 2.2 9.0 p = 0.017 | 25.8 (MR4, C2) 28.6 22.6 p = 0.35 | 63.3 61.6 65.3 p = 0.53 | 37.1 (5-yr EFS) 42.2 (5-yr EFS) 32.1 (5-yr EFS) p = 0.13 | 45.6 (5 yr) 48.3 (5 yr) 43.0 (5 yr) p = 0.37 |
| GRAALL(SAKK) GRAAPH-2014 NCT02611492 2016-2019 | NIL | Consolidation intensity: low (HD-MTX) vs high (HiDAC, HD-MTX) | 156 79 low (B) 77 high (A) | 47 (IQR 39-54) 47 (IQR 39-54) 49 (IQR 39-54) | 94.2 94.9 93.4 p = 0.74 | 3.2 (day 60) 2.5 3.9 p = 0.68 | 26.4 (MR4, C4) 24.1 28.9 p = 0.59 | 60.0 59.5 60.5 p = 0.97 | - 58.5 (4-yr RFS) 76.2 (4-yr RFS) p = 0.029 | - 73.4 (4 yr) 79.4 (4 yr) p = 0.27 |
| China CCCG-ALL2015 ChiCTR-IPR-14005706 2015-2018 | IM vs DAS | IM vs DAS with chemo | 189 97 IM 92 DAS | 7.8 (IQR 5-11) - - | 96.8 94.8 98.9 p = 0.21 | 1 death (IM arm) | - | None | - 48.9 (4-yr EFS) 71.0 (4-yr EFS) p = 0.005 | - 69.2 (4-yr) 88.4 (4-yr) p = 0.04 |
| Global PhALLCON NCT03589326 2018-2022 | IM vs PON | IM vs PON with low-intensity chemo | 245 81 IM 163 PON | 54 (19-82) 52 (19-75) 54 (19-82) | - | 0 | (MR4, C9) 44.9 62.1 | 32.7 37.0 30.5 | - Med EFS 29 mos Med EFS NR (HR 0.65, 95% CI 0.39-1.1) | - Med OS NR Med OS NR (HR 0.76, 95% CI 0.38-1.5) |
Chemo, chemotherapy; CR, complete remission; CMR, complete molecular remission; DAS, dasatinib; dex, dexamethasone; EFS, event-free survival; GRAALL, Group for Research on Adult Acute Lymphoblastic Leukemia; HD-MTX, high-dose methotrexate; HiDAC, high-dose ara-c; HR, hazard ratio; IM, imatinib; med, median; mos, months; MR, molecular response; NIL, nilotinib; NR, not reached; OS, overall survival; PON, ponatinib; RFS, relapse-free survival; SAKK (France, Belgium, and Switzerland); TKI, tyrosine kinase inhibitor; yr, year.