Phase 2
N=449
Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)
Chronic Myeloid Leukemia · Ph+ Acute Lymphoblastic Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT01207440 ↗Enrolled (actual)
449
Serious AEs
68.8%
Results posted
Jan 2020
Primary outcome: Primary: Percentage of CP-CML Participants With Major Cytogenetic Response (MCyR) — 50.7; 70.3 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Ponatinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Ariad Pharmaceuticals
- Primary completion
- Dec 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of CP-CML Participants With Major Cytogenetic Response (MCyR) |
50.7; 70.3 | — |
| PRIMARY Percentage of AP-CML Participants With Major Hematologic Response (MaHR) |
56.9; 55.6 | — |
| PRIMARY Percentage of BP-CML/Ph+ ALL Participants With MaHR |
35.4; 32.6 | — |
| SECONDARY Percentage of CP-CML Participants With CHR |
94.6; 92.2 | — |
| SECONDARY Percentage of CP-CML Participants With Confirmed MCyR |
40.9; 62.5 | — |
| SECONDARY Percentage of CP-CML Participants With Major Molecular Response (MMR) |
35.0; 57.8 | — |
| SECONDARY Percentage of AP-CML or BP-CML/Ph+ ALL Participants With MCyR |
33.8; 55.6; 27.1; 34.8 | — |
| SECONDARY Percentage of AP-CML or BP-CML/Ph+ ALL Participants With Confirmed MCyR |
24.6; 38.9; 20.8; 15.2 | — |
| SECONDARY Percentage of AP-CML or BP-CML/Ph+ ALL Participants With MMR |
18.5; 33.3; 18.8; 4.3 | — |
| SECONDARY Time to Response |
13.0; 10.0; 21.0; 20.5; 28.0; 24.0 | — |
| SECONDARY Duration of Response |
NA; NA; 360.0; 732.0; 196.0; 108.0 | — |
| SECONDARY Progression-free Survival (PFS) |
NA; 1809.0; 432.0; 959.0; 111.0; 83.0 | — |
| SECONDARY Overall Survival (OS) |
NA; NA; 1689.0; 1847.0; 209.0; 200.0 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Serious AE (SAE) |
203; 64; 65; 18; 48; 46 | — |
Summary
The purpose of this study is to determine the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast phase (BP) or with philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who either are resistant or intolerant to either dasatinib or nilotinib, or have the (T)hreonine-315-(I)soleucine (T315I) mutation.
Eligibility Criteria
Inclusion Criteria
- Participants must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL
- Previously treated with and developed resistance or intolerance to dasatinib or nilotinib OR developed the T3151 mutation after any tyrosine kinase inhibitor (TKI) therapy
- ≥18 years old
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Minimum life expectancy of ≥3 months
- Adequate kidney function
- Adequate liver function
- Normal pancreatic function
- Normal QT Fridericia-corrected interval (QTcF) ≤450 ms for males and ≤470 ms for females
- Negative pregnancy test (if woman of childbearing potential)
- Agree to use effective form of contraception (as applicable)
- Ability to comply with study procedures, in the Investigator's opinion
Exclusion Criteria
- Received prior TKI treatment within 7 days prior to receiving the first dose of ponatinib, or have not recovered from adverse events (except alopecia) due to agents previously administered.
- Received other therapies as follows:
- For CML chronic phase (CP) and accelerated phase (AP) participants, received hydroxyurea or anagrelide within 24 hours prior to receiving the first dose of ponatinib; interferon, cytarabine, or immunotherapy within 14 days prior to first dose of ponatinib; or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib.
- For CML blast phase (BP) participants, received chemotherapy within 14 days prior to the first dose of ponatinib.
- For Ph+ ALL participants, received corticosteroids within 24 hours before the first dose of ponatinib; or vincristine within 7 days prior to the first dose of ponatinib; or received other chemotherapy within 14 days prior to the first dose of ponatinib.
- Underwent stem cell transplant 450 mg/dL)
- Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of ponatinib
- Diagnosed with another primary malignancy in the past 3 years
- Pregnant or lactating
- Underwent major surgery within 14 days prior to first dose of ponatinib
- Have ongoing or active infection
- Suffer from any other condition or illness that would compromise safety or interfere with evaluation of the drug
Data sourced from ClinicalTrials.gov (NCT01207440). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.