Ignite Creation Date:
2025-12-24 @ 7:18 PM
Ignite Modification Date:
2026-01-03 @ 11:07 PM
Study NCT ID:
NCT02782403
Status:
TERMINATED
Last Update Posted:
2020-11-19
First Post:
2016-05-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Axitinib and Bosutinib in Treating Patients With Chronic, Accelerated, or Blastic Phase Chronic Myeloid Leukemia
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
Alternating or Combined Therapy With Axitinib and Bosutinib for Patients With Chronic Myeloid Leukemia in Chronic, Accelerated, or Blastic Phases
Status:
TERMINATED
Status Verified Date:
2020-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Terminated per PI's request at the time of CR. Study was closed due to low/slow accrual due to other competing studies.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I/II trial studies the side effects and best dose of axitinib and bosutinib and how well they work in treating patients with chronic, accelerated, or blastic phase chronic myeloid leukemia. Axitinib and bosutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description:
PRIMARY OBJECTIVES:
I. To assess the rate of major cytogenetic response (MCyR) of an alternating schedule of axitinib and bosutinib in patients with chronic myeloid leukemia, chronic phase (CML-CP) after failure of/intolerance to \>= 3 tyrosine kinase inhibitors (TKIs) using standard response criteria. (Chronic Phase Cohort) II. To determine the recommended phase II doses (RPTDs) of axitinib and bosutinib in combination in patients with chronic myeloid leukemia (CML) in accelerated phase (CML-AP) or blast phase (CML-BP). (Advanced phase \[AP\] patients must have received \>= 1 prior TKI). (Advanced Phase Cohort - Phase I Portion) III. To evaluate the rate of major hematologic response (MaHR) of combined treatment with axitinib and bosutinib in patients with CML-AP or CML-BP using standard response criteria. (AP patients must have received \>= 1 prior TKI). (Advanced Phase Cohort - Phase II Portion)
SECONDARY OBJECTIVES:
I. To determine the rate of complete cytogenetic response (CCyR), breast cancer gene (BCR-ABL/ABL) =\< 10% and =\< 1%, major molecular response (MMR), molecular response 4-log (MR4), molecular response 4.5-log (MR4.5), and complete molecular response (CMR), overall and at different time points. (Chronic Phase Cohort) II. To determine the duration of response (DOR), event-free survival (EFS), transformation-free survival (TFS), failure-free survival (FFS) and overall survival (OS) for patients with CML-CP treated with alternating axitinib and bosutinib after failure of/intolerance to \>= 3 TKIs. (Chronic Phase Cohort) III. To determine the safety and tolerability of alternating therapy with axitinib and bosutinib after failure of/intolerance to \>= 3 TKIs. (Chronic Phase Cohort) IV. To establish the response rate of concurrent administration of axitinib and bosutinib to patients with CML-AP or CML-BP. (AP patients must have received \>= 1 prior TKI). (Advanced Phase Cohort - Phase I Portion) V. To determine the rate of complete hematologic response (CHR), complete cytogenetic response (CCyR), BCR-ABL/ABL =\< 10% and =\< 1%, major molecular response (MMR), molecular response 4-log (MR4), molecular response 4.5-log (MR4.5), and complete molecular response (CMR), overall and at different time points of combined treatment with axitinib and bosutinib in patients with CML-AP or CML-BP. (AP patients must have received \>= 1 prior TKI). (Advanced Phase Cohort - Phase I Portion) VI. To determine the DOR, EFS, TFS, FFS and OS for patients with CML-AP or -BP treated with combined axitinib and bosutinib. (AP patients must have received \>= 1 prior TKI). (Advanced Phase Cohort - Phase II Portion) VII. To evaluate the probability of developing Abl kinase domain and other somatic mutations in patients with CML treated with alternating (CP) or concurrent (AP/BP) axitinib and bosutinib. (Advanced Phase Cohort - Phase II Portion) VIII. To analyze differences in response rates, duration and survival according to pre-treatment mutations and patient characteristics in both the CP and AP/BP cohorts. (Advanced Phase Cohort - Phase II Portion) IX. To characterize mechanisms of resistance in patients who develop resistance to alternating (CP) or concomitant (AP/BP) therapy with axitinib and bosutinib. (Advanced Phase Cohort - Phase II Portion) X. To evaluate symptom burden in patients with CML receiving axitinib and bosutinib, whether alternating (CP) or in combination (AP/BP). (Advanced Phase Cohort - Phase II Portion)
OUTLINE: This is a dose-escalation followed by a phase II study. Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients with chronic phase CML receive either bosutinib orally (PO) once a day (QD) or axitinib PO twice a day (BID) alone for 3 months. Patients then switch to the other drug for 3 months and alternate between the two every 3 months in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients with accelerated or blastic phase CML receive bosutinib PO QD and axitinib PO BID for 3 months. Courses repeat every 3 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1 month.
I. To assess the rate of major cytogenetic response (MCyR) of an alternating schedule of axitinib and bosutinib in patients with chronic myeloid leukemia, chronic phase (CML-CP) after failure of/intolerance to \>= 3 tyrosine kinase inhibitors (TKIs) using standard response criteria. (Chronic Phase Cohort) II. To determine the recommended phase II doses (RPTDs) of axitinib and bosutinib in combination in patients with chronic myeloid leukemia (CML) in accelerated phase (CML-AP) or blast phase (CML-BP). (Advanced phase \[AP\] patients must have received \>= 1 prior TKI). (Advanced Phase Cohort - Phase I Portion) III. To evaluate the rate of major hematologic response (MaHR) of combined treatment with axitinib and bosutinib in patients with CML-AP or CML-BP using standard response criteria. (AP patients must have received \>= 1 prior TKI). (Advanced Phase Cohort - Phase II Portion)
SECONDARY OBJECTIVES:
I. To determine the rate of complete cytogenetic response (CCyR), breast cancer gene (BCR-ABL/ABL) =\< 10% and =\< 1%, major molecular response (MMR), molecular response 4-log (MR4), molecular response 4.5-log (MR4.5), and complete molecular response (CMR), overall and at different time points. (Chronic Phase Cohort) II. To determine the duration of response (DOR), event-free survival (EFS), transformation-free survival (TFS), failure-free survival (FFS) and overall survival (OS) for patients with CML-CP treated with alternating axitinib and bosutinib after failure of/intolerance to \>= 3 TKIs. (Chronic Phase Cohort) III. To determine the safety and tolerability of alternating therapy with axitinib and bosutinib after failure of/intolerance to \>= 3 TKIs. (Chronic Phase Cohort) IV. To establish the response rate of concurrent administration of axitinib and bosutinib to patients with CML-AP or CML-BP. (AP patients must have received \>= 1 prior TKI). (Advanced Phase Cohort - Phase I Portion) V. To determine the rate of complete hematologic response (CHR), complete cytogenetic response (CCyR), BCR-ABL/ABL =\< 10% and =\< 1%, major molecular response (MMR), molecular response 4-log (MR4), molecular response 4.5-log (MR4.5), and complete molecular response (CMR), overall and at different time points of combined treatment with axitinib and bosutinib in patients with CML-AP or CML-BP. (AP patients must have received \>= 1 prior TKI). (Advanced Phase Cohort - Phase I Portion) VI. To determine the DOR, EFS, TFS, FFS and OS for patients with CML-AP or -BP treated with combined axitinib and bosutinib. (AP patients must have received \>= 1 prior TKI). (Advanced Phase Cohort - Phase II Portion) VII. To evaluate the probability of developing Abl kinase domain and other somatic mutations in patients with CML treated with alternating (CP) or concurrent (AP/BP) axitinib and bosutinib. (Advanced Phase Cohort - Phase II Portion) VIII. To analyze differences in response rates, duration and survival according to pre-treatment mutations and patient characteristics in both the CP and AP/BP cohorts. (Advanced Phase Cohort - Phase II Portion) IX. To characterize mechanisms of resistance in patients who develop resistance to alternating (CP) or concomitant (AP/BP) therapy with axitinib and bosutinib. (Advanced Phase Cohort - Phase II Portion) X. To evaluate symptom burden in patients with CML receiving axitinib and bosutinib, whether alternating (CP) or in combination (AP/BP). (Advanced Phase Cohort - Phase II Portion)
OUTLINE: This is a dose-escalation followed by a phase II study. Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients with chronic phase CML receive either bosutinib orally (PO) once a day (QD) or axitinib PO twice a day (BID) alone for 3 months. Patients then switch to the other drug for 3 months and alternate between the two every 3 months in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients with accelerated or blastic phase CML receive bosutinib PO QD and axitinib PO BID for 3 months. Courses repeat every 3 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1 month.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: