A Phase I/II Study to Determine the Safety and Efficacy of Ruxolitinib, a JAK1/JAK2 Inhibitor, in Subjects With Relapsed or Refractory Acute Leukemia
14 Years
N/A
Both
Leukemia
Trial Information
A Phase I/II Study to Determine the Safety and Efficacy of Ruxolitinib, a JAK1/JAK2 Inhibitor, in Subjects With Relapsed or Refractory Acute Leukemia
The Study Drug:
Ruxolitinib is designed to block a gene mutation that may be important in cancer cell growth
and survival. By blocking the gene mutation, this may cause the cancer cells to die.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. Up to 30 participants will be enrolled in the
Phase I portion of the study, and up to 136 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of ruxolitinib you receive will depend
on when you joined this study. The first group of participants will receive the lowest dose
level of ruxolitinib. Each new group will receive a higher dose of ruxolitinib than the
group before it, if no intolerable side effects were seen. This will continue until the
highest tolerable dose of ruxolitinib is found.
If you are enrolled in the Phase II portion, you will receive ruxolitinib at the highest
dose that was tolerated in the Phase I portion or at a lower dose.
Study Drug Administration:
You will take ruxolitinib tablet(s) by mouth 2 times a day on Days 1-28 of each 28-day study
cycle.
You will be asked to keep a diary to record the doses taken. You will be asked to bring
your diary and any unused drug to your next visit.
Study Visits:
On Days 1, 7, 14, and 21 of Cycle 1:
- You will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- You will be asked about any treatments you may have had, any other drugs you may be
taking, and any side effects you may be having.
- On Day 14 only, you will have a bone marrow aspiration performed to check the status of
the disease.
On Day 1 of Cycle 2:
- You will have a physical exam.
- You will be asked about any treatments you may have had, any other drugs you may be
taking, and any side effects you may be having.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- You will have a bone marrow aspiration performed to check the status of the disease.
During Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine tests at
least every 1-2 weeks. This blood may be drawn at a clinic close to your home.
On Day 1 of Cycles 3, 6, 9, and beyond:
- You will have a physical exam.
- You will be asked about any treatments you may have had, any other drugs you may be
taking, and any side effects you may be having.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- You will have a bone marrow aspiration performed to check the status of the disease. On
Day 1 of Cycle 3, this will only be done if your doctor thinks it is needed.
Length of Study:
You may continue taking the study drug for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug if the disease gets worse or
intolerable side effects occur.
Your participation on the study will be over once you have completed the end-of-study visit
and the follow-up call.
End-of-Study Visit:
After your last dose of study drug, you will have an end-of-study visit. At this visit, the
following tests and procedures will be performed:
- You will have a physical exam.
- You will be asked about any treatments you may have had, any other drugs you may be
taking, and any side effects you may be having.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- You will have a bone marrow aspiration performed to check the status of the disease.
Follow-Up:
About one month after your end-of-study visit, the study staff will call and ask about any
side effects you may be having. This call should last about 5 minutes.
This is an investigational study. Ruxolitinib is FDA approved and commercially available
for the treatment of intermediate or high-risk myelofibrosis, including primary
myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential
thrombocythemia (post-ET) myelofibrosis. Its use to treat acute leukemia is
investigational.
Up to 166 patients will take part in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:
1. Must be >14 years of age
2. Must be diagnosed with refractory or relapsed AML or ALL.
3. Must have adequate organ function as demonstrated by the following: o ALT (SGOT)
and/or AST (SGPT) equal to or less than 1.5x upper limit of normal o Serum creatinine
equal to or less than 2.5 mg/dL
4. ECOG performance status (PS) of 0, 1, or 2
5. At least 2 weeks from prior leukemia-directed treatment to starting treatment drug
(except for hydroxyurea, which is allowed if clinically indicated but should be
stopped after 2 weeks of receiving study drug, and glucocorticoids, which are allowed
but should be stopped upon starting treatment drug).
6. Treatment-related toxicities from prior therapies must have resolved to Grade equal
to or less than 1 (except for peripheral neuropathy, which should resolve to grade
equal to or less than 2)
7. No active malignancies with the exception of basal cell or squamous cell carcinoma of
the skin, or carcinoma "in situ" of the cervix or breast.
8. Females of childbearing potential (FCBP)(A female of childbearing potential is a
sexually mature woman who: 1) has not undergone a hysterectomy or bilateral
oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive
months (i.e., has had menses at any time in the preceding 24 consecutive months) must
have negative pregnancy test. FCBP and males participating in the study must agree to
use a reliable form of contraception or to practice complete abstinence from
heterosexual intercourse while participating in the study and for at least 28 days
after discontinuation from the study. If pregnancy or a positive pregnancy test does
occur in a study subject, treatment with the study drug must be immediately
discontinued.
Exclusion Criteria:
1. Known positive status for HIV, or known active hepatitis A, B, or C infection.
2. Any serious medical condition or psychiatric illness that would prevent, (as judged
by the treating physician) the subject from signing the informed consent form or any
condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.
3. Pregnant or lactating females.
4. Acute promyelocytic leukemia
5. Concurrent use of strong inducers or strong inhibitors of CYP3A4. Strong inducers are
rifampin and St. John's Worth. Strong inhibitors are HIV-antivirals, clarythromycin,
itraconazole, ketoconazole, nefazodone, and telithromycin.
6. Participating in any other research trial.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum Tolerated Dose
Outcome Time Frame:
14 days
Safety Issue:
Yes
Principal Investigator
Srdan Verstovsek, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2010-0450
NCT ID:
NCT01251965
Start Date:
December 2010
Completion Date:
Related Keywords:
- Leukemia
- Relapsed Acute Leukemia
- Acute myeloid leukemia
- AML
- Acute lymphocytic leukemia
- ALL
- Ruxolitinib
- Jakafi
- INC424
- INCB018424
- Leukemia
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
