Evaluation Of Ruxolitinib And Azacytidine Combination As A Therapy For Patients With Myelofibrosis And Myelodysplastic Syndrome/ Myeloproliferative Neoplasm
18 Years
N/A
Both
Leukemia
Trial Information
Evaluation Of Ruxolitinib And Azacytidine Combination As A Therapy For Patients With Myelofibrosis And Myelodysplastic Syndrome/ Myeloproliferative Neoplasm
Study Treatment:
If you are found to be eligible to take part in this study, you will take ruxolitinib 2
times every day by mouth. If you miss or vomit your dose of ruxolitinib, do not make up the
dose.
Beginning with Cycle 4, on Days 1-5, you will receive azacytidine either under the skin or
through a needle in your vein.
Beginning with Cycle 4, on Days 1-5, Your dose of ruxolitinib and/or azacytidine may be
raised, lowered, and/or delayed if the doctor thinks it is in your best interest.
You will be given a drug diary and asked to write down what time you take the study drugs.
Bring in any unused study drugs and bottles to each study visit.
Each cycle is 28 days.
Study Visits:
Each study visit may be performed at +/- 3 days than the day stated.
On Day 1 of Cycles 1-7 and then every 3 cycles:
- You will be asked if you have had any side effects.
- You will have a physical exam, including measurement of your vital signs and weight.
- Your spleen and liver will be measured.
- You will complete 2 questionnaires about how you are feeling.
On Day 1 of Cycles 1-6 and then every 3 cycles, your complete medical history will be
recorded.
Once a week during Cycles 1, 2, and 4, every 2 weeks during Cycles 3 and 6, and then 1 time
each month after that, blood (about 2-3 tablespoons) will be drawn for routine tests.
If the doctor thinks it is needed, after Cycles 6 and 12, you will have a bone marrow
aspiration to check the status of the disease.
Research Blood Tests:
Extra blood will be drawn for pharmacokinetic (PK) testing and pharmacodynamic (PD). PK
testing measures the amount of study drug in the body at different time points. PD testing
measures how the level of study drug in your body may affect the disease.
Blood (about 2-3 teaspoons each time) will be drawn for PK testing:
- On Day 1 of Cycle 1, before you receive the study drug, and then 1, 2, and 5 hours
later
- On Day 1 of Cycle 6, before you receive the study drug, and then 1, 2, and 5 hours
later
- On Day 1 of Cycle 12 (or at the end of study if you go off study early), before you
receive the study drug, and then 1, 2, and 5 hours later
Blood (about 2-3 teaspoons each time) will be drawn for PD testing:
- On Day 1 of Cycle 1, before you receive the study drug and then 2 hours later
- On Day 1 of Cycle 3, before you receive the study drug
- On Day 1 of Cycle 6, before you receive the study drug and then 2 hours later
- On Day 1 of Cycle 9, before you receive the study drug
- On Day 1 of Cycle 12 (or at the end of study if you go off study early), before you
receive the study drug and then 2 hours later
Length of Study:
You can take up to 15 cycles of ruxolitinib and 12 cycles of azacytidine. After 15 cycles of
ruxolitinib, if your doctor thinks it is in your best interest, you may continue taking it
off study. You will no longer be able to take the study drugs if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.
You will be called about 30 days after you go off study and asked if you have had any side
effects and/or any new treatment(s).
This is an investigational study. Ruxolitinib is FDA approved and commercially available to
treat myelofibrosis. Azacytidine is FDA approved and commercially available for
myelodysplastic syndrome. The combination of ruxolitinib and azacytidine to treat
myelofibrosis and myelodysplastic syndrome/myeloproliferative neoplasm is investigational.
Up to 50 participants will be enrolled in this study. All will take part at MD Anderson.
Inclusion Criteria:
1. Patients with diagnosis of myelofibrosis {either primary, post polycythemia vera, or
post essential thrombocythemia myelofibrosis (PMF, PPV MF, or PET MF) requiring
therapy, including previously treated and relapsed or refractory, or if newly
diagnosed, with intermediate-1 or -2 or high risk according to International Working
Group (IWG-MRT) criteria. Patients with a diagnosis of MDS/MPN requiring therapy
{including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia
(BCR-ABL1 negative; aCML), and myelodysplastic syndrome/myeloproliferative neoplasm,
unclassifiable (MDS/MPN-U)} that require therapy.
2. Understanding and voluntarily signing an IRB-approved informed consent form.
3. Age >/= 18 years at the time of signing informed consent
4. ECOG performance status 0 to 2.
5. Adequate liver function (direct bilirubin of ULN if related to MF or MDS/MPN associated liver infiltration): if total bilirubin
is
6. Creatinine
7. Platelets >/= 100 x 109/L
8. Absolute neutrophil count (ANC) >/= 1.0 x 109/L
Exclusion Criteria:
1. Use of any other standard drug (e.g. hydroxyurea, anagrelide, growth factors) or
experimental drug or therapy within 14 days of starting study therapy and/or lack of
recovery from all toxicity from previous therapy to grade 1 or better. Hydroxyurea
for patients with rapidly proliferative disease( at the discretion of the treating
physician) can be used up to 24 hours prior to therapy but not concomitantly with RUX
or AZA.
2. Patients previously treated with RUX or AZA are not eligible.
3. Any serious psychological condition or psychiatric illness that would prevent the
subject from signing the informed consent document, in the investigator opinion.
4. Pregnant or lactating females or suspected pregnancy
5. Subjects of childbearing potential who are unwilling to take appropriate precautions
(from screening through follow-up) to avoid becoming pregnant or fathering a child. •
Females of non-childbearing potential are defined as women who (a 55 years of age
with history of amenorrhea for 1 year, OR (b) are surgically sterile for at least 3
months. • For females of childbearing potential, or for males, pregnancy must be
avoided by taking appropriate precautions. These precautions and the methods of
contraception should be communicated to the subjects and their understanding
confirmed.
6. 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.
7. Known positive for HIV or with active infectious hepatitis, type A, B or C
8. Patients with active malignancy of other type than required for this study, are not
eligible.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
Outcome Measure:
Number of participants with Objective Response
Outcome Description:
Objective response, defined as CR (complete remission/response) + PR (partial remission/response)+ CI (clinical improvement) for MF patients (arm 1) and CR + PR + HI (hematologic improvement) for MDS/MPN patients (arm 2). Complete Response: No symptoms related to MDS/MPN and absolute neutrophil count >1x109/L and platelet count >100 x109/L, and normal marrow differential (< 5% blasts). Partial Response: CR with 6-25% abnormal cells in marrow or 50% decrease in bone marrow blasts. CR partial (CRp): As per CR but platelet count <100 x109/L. Hematologic Improvement (HI): Hematologic improvement described by the number of individual positively affected cell lines.
Outcome Time Frame:
Following 6 treatment cycles of 28 days
Safety Issue:
No
Principal Investigator
Naval Daver, MD
Investigator Role:
Study Chair
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2012-0737
NCT ID:
NCT01787487
Start Date:
March 2013
Completion Date:
Related Keywords:
- Leukemia
- Leukemia
- Myelofibrosis
- Myelodysplastic syndrome
- Myeloproliferative neoplasm
- Ruxolitinib
- RUX
- Jakafi
- INCB018424
- INC424
- Azacitidine
- AZA
- 5-Azacitidine
- 5-aza
- Vidaza
- 5-AZC
- AZA-CR
- Ladakamycin
- NSC-102816
- Primary Myelofibrosis
- Neoplasms
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
