Bosutinib Dose-Optimization Study in Chronic Myeloid Leukemia (CML)
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Blood Cancer, Blood Cancer, Hematology |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/6/2019 |
| Start Date: | October 2016 |
| End Date: | October 2022 |
An Open-Label Phase II Dose Optimization Study of Bosutinib at a Starting Dose of 300 mg Daily for Adult Patients With Chronic Myeloid Leukemia (CML) in Chronic Phase Post Frontline Tyrosine Kinase Inhibitor (TKI) Failure
Bosutinib is a type of tyrosine kinase inhibitor (TKI) which is commonly used for the
treatment of chronic phase chronic myelogenous leukemia (CP CML). The standard dose of
bosutinib often causes temporary, but severe, diarrhea which goes away after bosutinib is
stopped or the dose is lowered.
The goal of this clinical research study it to learn if a lower dose of bosutinib is as
effective as the standard dose. Researchers think that by starting with a lower dose of
bosutinib and slowly increasing the dose (if needed), the likelihood and severity of diarrhea
and other side effects may be lowered in patients with CP CML.
To help researchers learn if the lower dose of bosutinib is as effective as the regular dose,
researchers will test your cytogenetic response to the drug. Cytogenetic testing looks at how
genetic changes to cells (in this study, the BRC-ABL protein and Philadelphia chromosome) may
affect how the disease may react to the study drug.
This is an investigational study. This is an investigational study. Bosutinib is FDA approved
and commercially available for the treatment of chronic phase CML. It is considered
investigational to use bosutinib at a lower dose compared to the standard dose.
The study doctor can explain how the study drug is designed to work.
Up to 42 participants will take part in this study. All will be enrolled at MD Anderson.
treatment of chronic phase chronic myelogenous leukemia (CP CML). The standard dose of
bosutinib often causes temporary, but severe, diarrhea which goes away after bosutinib is
stopped or the dose is lowered.
The goal of this clinical research study it to learn if a lower dose of bosutinib is as
effective as the standard dose. Researchers think that by starting with a lower dose of
bosutinib and slowly increasing the dose (if needed), the likelihood and severity of diarrhea
and other side effects may be lowered in patients with CP CML.
To help researchers learn if the lower dose of bosutinib is as effective as the regular dose,
researchers will test your cytogenetic response to the drug. Cytogenetic testing looks at how
genetic changes to cells (in this study, the BRC-ABL protein and Philadelphia chromosome) may
affect how the disease may react to the study drug.
This is an investigational study. This is an investigational study. Bosutinib is FDA approved
and commercially available for the treatment of chronic phase CML. It is considered
investigational to use bosutinib at a lower dose compared to the standard dose.
The study doctor can explain how the study drug is designed to work.
Up to 42 participants will take part in this study. All will be enrolled at MD Anderson.
Study Drug Administration:
Each study cycle is 28 days.
You will take bosutinib tablets by mouth 1 time each morning every cycle while you are on
study. You should take your dose of study drug with breakfast and a small cup of water (about
6 ounces).
If you miss or vomit a dose of bosutinib, do not retake the dose. Wait and take your next
dose as scheduled.
If the study doctor thinks it is in your best interest, the dose of study drug you receive
may be raised or lowered, depending on how you react to the study drug.
Study Visits:
On Day 15 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests. If your
doctor thinks it is appropriate to do so, you may have this blood drawn at a local lab or
doctor's office closer to your home. The results will be sent to the study doctor for review.
The study doctor or study staff may also call you to discuss the results of the blood draw
and to ask how you are doing. This call should last about 5-10 minutes.
On Day 28 of Cycle 1:
- You will have a physical exam.
- Blood (about 3-4 teaspoons) will be drawn for routine tests.
- You will have an EKG.
On Day 28 of Cycle 2:
- Blood (about 3-4 teaspoons) will be drawn for routine tests.
- If your doctor thinks it is appropriate to do so, you may have this blood drawn at a
local lab or doctor's office closer to your home. The results will be sent to the study
doctor for review. The study doctor or study staff may also call you to discuss the
results of the blood draw and to ask how you are doing. This call should last about 5-10
minutes.
On Day 28 of Cycles 3, 9, 12, 15, 18, 21 and 24:
- You will have a physical exam.
- Blood (about 3-4 teaspoons) will be drawn for routine tests, genetic biomarkers, and
BCR-ABL level testing. Biomarkers are found in the blood/tissue and may be related to
your reaction to the study drug.
On Day 28 of Cycle 6, you will have a bone marrow aspirate for cytogenetic testing and to
check the status of the disease. If your doctor thinks it is needed, you may have this
repeated later in the study.
If the disease appears to get worse and the doctor thinks it is needed, these
tests/procedures may be repeated at any time to check the status of the disease.
Length of Study:
You may continue taking the study drug for up to 2 years. If the doctor thinks it is in your
best interest, you may be able to continue taking bosutinib at the dose you were taking at
the end of the study, as part of your regular care. You will no longer be able to take the
study drug if the disease gets worse, if intolerable side effects occur, or if you are unable
to follow study directions.
Your participation on this study will be over after long-term follow-up has been completed.
End-of-Study Visit:
If you stopped taking the study drug before Cycle 24, within 7-28 days after your last dose
of study drug:
- You will have a physical exam.
- Blood (about 3-4 teaspoons) will be drawn for routine tests and for BCR-ABL level
testing.
- You will have a bone marrow aspirate for cytogenetic testing, to check the status of the
disease, and to check for genetic mutations.
- You will have either an ECHO or MUGA scan.
Long-Term Follow-Up:
You will be called by a member of the study staff every 12 weeks for up to 2 years and then
every 24 weeks after that for the next 2 years. During these calls, you will be asked how you
are doing, if you have started any other anti-cancer treatment, and about any side effects
you may be having. After that, you will be called 4 times each year until the study ends or
you withdraw from the study. Each phone call should last about 5-10 minutes.
If the doctor thinks it is in your best interest, you may come back to the clinic for
additional follow-up, as part of your standard treatment.
Each study cycle is 28 days.
You will take bosutinib tablets by mouth 1 time each morning every cycle while you are on
study. You should take your dose of study drug with breakfast and a small cup of water (about
6 ounces).
If you miss or vomit a dose of bosutinib, do not retake the dose. Wait and take your next
dose as scheduled.
If the study doctor thinks it is in your best interest, the dose of study drug you receive
may be raised or lowered, depending on how you react to the study drug.
Study Visits:
On Day 15 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests. If your
doctor thinks it is appropriate to do so, you may have this blood drawn at a local lab or
doctor's office closer to your home. The results will be sent to the study doctor for review.
The study doctor or study staff may also call you to discuss the results of the blood draw
and to ask how you are doing. This call should last about 5-10 minutes.
On Day 28 of Cycle 1:
- You will have a physical exam.
- Blood (about 3-4 teaspoons) will be drawn for routine tests.
- You will have an EKG.
On Day 28 of Cycle 2:
- Blood (about 3-4 teaspoons) will be drawn for routine tests.
- If your doctor thinks it is appropriate to do so, you may have this blood drawn at a
local lab or doctor's office closer to your home. The results will be sent to the study
doctor for review. The study doctor or study staff may also call you to discuss the
results of the blood draw and to ask how you are doing. This call should last about 5-10
minutes.
On Day 28 of Cycles 3, 9, 12, 15, 18, 21 and 24:
- You will have a physical exam.
- Blood (about 3-4 teaspoons) will be drawn for routine tests, genetic biomarkers, and
BCR-ABL level testing. Biomarkers are found in the blood/tissue and may be related to
your reaction to the study drug.
On Day 28 of Cycle 6, you will have a bone marrow aspirate for cytogenetic testing and to
check the status of the disease. If your doctor thinks it is needed, you may have this
repeated later in the study.
If the disease appears to get worse and the doctor thinks it is needed, these
tests/procedures may be repeated at any time to check the status of the disease.
Length of Study:
You may continue taking the study drug for up to 2 years. If the doctor thinks it is in your
best interest, you may be able to continue taking bosutinib at the dose you were taking at
the end of the study, as part of your regular care. You will no longer be able to take the
study drug if the disease gets worse, if intolerable side effects occur, or if you are unable
to follow study directions.
Your participation on this study will be over after long-term follow-up has been completed.
End-of-Study Visit:
If you stopped taking the study drug before Cycle 24, within 7-28 days after your last dose
of study drug:
- You will have a physical exam.
- Blood (about 3-4 teaspoons) will be drawn for routine tests and for BCR-ABL level
testing.
- You will have a bone marrow aspirate for cytogenetic testing, to check the status of the
disease, and to check for genetic mutations.
- You will have either an ECHO or MUGA scan.
Long-Term Follow-Up:
You will be called by a member of the study staff every 12 weeks for up to 2 years and then
every 24 weeks after that for the next 2 years. During these calls, you will be asked how you
are doing, if you have started any other anti-cancer treatment, and about any side effects
you may be having. After that, you will be called 4 times each year until the study ends or
you withdraw from the study. Each phone call should last about 5-10 minutes.
If the doctor thinks it is in your best interest, you may come back to the clinic for
additional follow-up, as part of your standard treatment.
Inclusion Criteria:
1. Patients with CML in chronic phase who have resistance and/or intolerance to frontline
TKI therapy. Resistance is defined as lack (lack defined as response not achieved or
lost by the given dates mentioned hereafter) of CHR (complete hematologic response)
within 3 months, lack of MCyR within 6 months, and lack of CCyR within 12 months of
therapy with frontline TKIs. In addition, loss of MCyR, CCyR or MMR at any time during
the course of therapy is also considered resistance to therapy. Intolerance is defined
as persistent or severe toxicity that is unacceptable to the patient.
2. Chronic phase disease is defined as: a. <15% blasts in peripheral blood and bone
marrow; b. <30% blasts plus promyelocytes in peripheral blood and bone marrow; c. <20%
basophils in peripheral blood; d. > or = 100 x 10^9/L platelets (> or = 100,000/mm^3);
e. No evidence of extramedullary disease except hepatosplenomegaly; and f. No prior
diagnosis of AP or BP-CML. Patients with clonal evolution but no other criteria for
accelerated phase are eligible.
3. ECOG performance status of 0, 1, or 2.
4. Age 18 years or older.
5. Adequate organ function with creatinine less than or equal to 2.0 mg/dl, bilirubin
less than or equal to 2.0 mg/dl and ALT less than or equal to 3 times institutional
upper limit of normal
6. Females of childbearing potential must have a negative serum or urine beta human
chorionic gonadotrophin (beta-hCG) pregnancy test result within 14 days prior to the
first dose of study drugs and must agree to use one of the following effective
contraception methods during the study and for 30 days following the last dose of
study drug. Effective methods of birth control include: a. birth control pills, shots
or implants (placed under the skin by a health care provider) or patches (placed on
the skin); b. Intrauterine devices (IUDs); c. condom or occlusive cap (diaphragm or
cervical/vault caps) used with spermicide. Females of non-childbearing potential are
those who are postmenopausal greater than 1 year or who have had a bilateral tubal
ligation or hysterectomy.
7. Males who have partners of childbearing potential must agree to use an effective
contraceptive method during the study and for 30 days following the last dose of study
drug.
8. Patients or their legally authorized representative must provide written informed
consent.
Exclusion Criteria:
1. Women that are pregnant or lactating.
2. Known to be HIV+.
3. Active and uncontrolled disease/infection that in the opinion of the treating
physician and principal investigator may affect the ability to participate in the
trial or put the patient at unduly high risk.
4. Unable or unwilling to sign the informed consent document.
5. Received other investigational therapy within the past 14 days
6. Presence of T315I mutation by ABL1 sequencing
7. Patient is currently in complete cytogenetic remission (CCyR).
We found this trial at
1
site
1515 Holcombe Blvd
Houston, Texas 77030
Houston, Texas 77030
713-792-2121
University of Texas M.D. Anderson Cancer Center The mission of The University of Texas MD...
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