PACE
A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias
Phase 2N = 449NCT01207440
- Population
- Heavily pretreated CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib, or with the BCR-ABL T315I mutation
- Design
- Open-label, multinational single-arm phase 2 trial (66 sites); ponatinib at an initial dose of 45 mg once daily; median follow-up 15 months in the primary report. Dose reductions to reduce arterial occlusive risk were implemented in October 2013, after the primary data cut.
- Primary endpoint
- MCyR, MaHR
- Arms
- Chronic-phase CML (evaluable) (experimental, n = 267): Ponatinib 45 mg once daily (initial dose)
- Chronic phase, resistant or intolerant (subgroup of the chronic-phase cohort) (experimental): Ponatinib 45 mg once daily (initial dose)
- Chronic phase, T315I mutation (subgroup of the chronic-phase cohort) (experimental): Ponatinib 45 mg once daily (initial dose)
- Accelerated-phase CML (experimental, n = 83): Ponatinib 45 mg once daily (initial dose)
- Blast-phase CML (experimental, n = 62): Ponatinib 45 mg once daily (initial dose)
- Ph-positive ALL (experimental, n = 32): Ponatinib 45 mg once daily (initial dose)
- People
- Cortes JE, PACE Investigators
Show the numbers
| Endpoint | Analysis | Chronic-phase CML (evaluable) / Chronic phase, resistant or intolerant (subgroup of the chronic-phase cohort) / Chronic phase, T315I mutation (subgroup of the chronic-phase cohort) / Accelerated-phase CML / Blast-phase CML / Ph-positive ALL | Control | Effect |
|---|---|---|---|---|
| MCyRChronic-phase CML (267 evaluable patients); subgroups as labelledMajor cytogenetic response at any time within the first 12 months (primary end point in chronic-phase CML) | primarymedian follow-up 15 monthsCortes 2013 | 56% | — | The estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. |
| CCyRChronic-phase CML (267 evaluable patients); subgroups as labelled | primarymedian follow-up 15 monthsCortes 2013 | 46% | — | — |
| MMRChronic-phase CML (267 evaluable patients); subgroups as labelled | primarymedian follow-up 15 monthsCortes 2013 | 34% | — | — |
| MaHRAccelerated-phase CML (83), blast-phase CML (62) and Ph-positive ALL (32)Major hematologic response at any time within the first 6 months (primary end point in accelerated-phase CML, blast-phase CML and Ph-positive ALL) | primarymedian follow-up 15 monthsCortes 2013 | 55% | — | — |
| MCyRAccelerated-phase CML (83), blast-phase CML (62) and Ph-positive ALL (32) | primarymedian follow-up 15 monthsCortes 2013 | 39% | — | — |
| MCyREvaluable chronic-phase CML patients (267 of 270 in the chronic-phase analysis) | finalmedian follow-up 56.8 monthsCortes 2018 | 60% | — | The probability of maintaining MCyR for 5 years was 82% among responders. |
| MMREvaluable chronic-phase CML patients (267 of 270 in the chronic-phase analysis) | finalmedian follow-up 56.8 monthsCortes 2018 | 40% | — | — |
| MR4.5Evaluable chronic-phase CML patients (267 of 270 in the chronic-phase analysis) | finalmedian follow-up 56.8 monthsCortes 2018 | 24% | — | — |
| OSChronic-phase CML patients in the final analysis (n = 270)Estimated 5-year overall survival | finalmedian follow-up 56.8 monthsCortes 2018 | 73% at 5 y | — | Single-arm trial; no comparison arm. |
| Endpoint | Analysis | Chronic-phase CML (evaluable) / Chronic phase, resistant or intolerant (subgroup of the chronic-phase cohort) / Chronic phase, T315I mutation (subgroup of the chronic-phase cohort) / Accelerated-phase CML / Blast-phase CML / Ph-positive ALL | Control | Effect |
|---|---|---|---|---|
| MCyRChronic-phase CML (267 evaluable patients); subgroups as labelledMajor cytogenetic response at any time within the first 12 months (primary end point in chronic-phase CML) | primarymedian follow-up 15 monthsCortes 2013 | 56% | — | The estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. |
| CCyRChronic-phase CML (267 evaluable patients); subgroups as labelled | primarymedian follow-up 15 monthsCortes 2013 | 46% | — | — |
| MMRChronic-phase CML (267 evaluable patients); subgroups as labelled | primarymedian follow-up 15 monthsCortes 2013 | 34% | — | — |
| MaHRAccelerated-phase CML (83), blast-phase CML (62) and Ph-positive ALL (32)Major hematologic response at any time within the first 6 months (primary end point in accelerated-phase CML, blast-phase CML and Ph-positive ALL) | primarymedian follow-up 15 monthsCortes 2013 | 55% | — | — |
| MCyRAccelerated-phase CML (83), blast-phase CML (62) and Ph-positive ALL (32) | primarymedian follow-up 15 monthsCortes 2013 | 39% | — | — |
| MCyREvaluable chronic-phase CML patients (267 of 270 in the chronic-phase analysis) | finalmedian follow-up 56.8 monthsCortes 2018 | 60% | — | The probability of maintaining MCyR for 5 years was 82% among responders. |
| MMREvaluable chronic-phase CML patients (267 of 270 in the chronic-phase analysis) | finalmedian follow-up 56.8 monthsCortes 2018 | 40% | — | — |
| MR4.5Evaluable chronic-phase CML patients (267 of 270 in the chronic-phase analysis) | finalmedian follow-up 56.8 monthsCortes 2018 | 24% | — | — |
| OSChronic-phase CML patients in the final analysis (n = 270)Estimated 5-year overall survival | finalmedian follow-up 56.8 monthsCortes 2018 | 73% at 5 y | — | Single-arm trial; no comparison arm. |
Appears in
Sources
Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369(19):1783-96.
Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132(4):393-404.