The goal of this clinical research study is to learn if ruxolitinib or dasatinib in
combination with chemotherapy can help to control Philadelphia Chromosome (Ph)-like acute
lymphoblastic leukemia (ALL). The safety of these drug combinations will also be studied.
If you are found to be eligible to take part in this study, you will be assigned to 1 of 2
study groups, based on the molecular type of the disease. You and the study staff will know
which study drug you will receive:
- Participants in Group A will receive ruxolitinib.
- Participants in Group B will receive dasatinib.
Study Drug Administration:
Each study cycle is 21 days.
Participants in Group A will take ruxolitinib tablets by mouth 2 times a day (about 12 hours
apart), with or without food.
Participants in Group B will take dasatinib tablets by mouth 1 time each day, with or without
food. You should take the study drug at the same time each day.
If your doctor thinks it is needed, you may receive steroids and/or hydroxyurea if your white
blood cell counts are too high.
If the disease responds to treatment with either ruxolitinib or dasatinib alone, you will
continue to receive that drug by itself. That first cycle of therapy will be called Cycle 0.
Your next cycle of dasatinib or ruxolitinib alone will continue to be called Cycle 0. Once
you move to intensive chemotherapy (described below), that first cycle will be called Cycle
If the disease does not respond to treatment by the end of the first cycle with ruxolitinib
or dasatinib, you will also receive up to 2½ years of chemotherapy treatment. You will
receive 8 cycles of intensive chemotherapy, using 2 different chemotherapy schedules. Once
you complete intensive chemotherapy, you will receive up to 2 years of maintenance
During intensive chemotherapy and maintenance chemotherapy, you may continue taking
ruxolitinib or dasatinib every day, for as long as you are receiving benefit and you are not
having intolerable side effects.
Chemotherapy is given several different ways:
- By mouth
- By vein, through a central venous catheter (CVC): A CVC is a sterile flexible tube that
will be placed into a large vein while you are under local anesthesia. Your doctor will
explain this procedure to you in more detail, and you will be required to sign a
separate consent form for this procedure.
- Intrathecal administration, through a lumbar puncture (spinal tap): A spinal tap (also
called a lumbar puncture) is when fluid surrounding the spinal cord is removed by
inserting a needle into the lower back. The affected area is numbed with local
anesthetic during the procedure. It can also be used to give chemotherapy. The number of
doses you receive will depend on how many doses the study doctor thinks is needed.
Occasionally, a sample of the fluid obtained from the spinal taps may be tested for
Your chemotherapy doses may be raised or lowered, depending on side effects. You will receive
other drugs during chemotherapy to help prevent or lower the risk of certain side effects,
including tumor lysis syndrome (breakdown products of the cancer cells entering the blood
stream, which may cause possible weakness, low blood pressure, muscle cramps, kidney damage,
and/or other organ damage).
You will receive several drugs (listed below) as part of your chemotherapy. Each cycle of
intensive chemotherapy is 21 days.
You may receive up to 8 cycles of intensive chemotherapy in the hospital. You will need to
stay in the hospital for the first 4-5 days of each cycle.
Hyper-CVAD: Cycles 1, 3, 5, and 7:
- On Days 1-3 of these cycles, you will receive cyclophosphamide by vein over about 3
hours, 2 times a day (about every 12 hours).
- On Days 1-3 of these cycles, starting about 1 hour before your cyclophosphamide
infusion, you will receive MESNA by vein over about 16 hours. MESNA is given to lower
the risk of side effects.
- On Day 4 of these cycles, you will receive doxorubicin by vein over 24-48 hours. On Days
4 and 11 (+/- 2 days) of these cycles, you will receive vincristine by vein over about
- On Days 1-4 and 11-14 (+/- 2 days) of these cycles, you will take dexamethasone by mouth
1 time a day or by vein over 30 minutes.
- If the doctor thinks it is needed, on Days 1 and 11 of Cycles 1 and 3 only, you may also
receive rituximab by vein over several hours.
Methotrexate alternating with cytarabine by vein: Cycles 2, 4, 6, and 8:
- On Day 1 of these cycles, you will receive methotrexate by vein over about 24 hours (+/-
- On Days 2-5 of these cycles, you will receive leucovorin by vein over or by mouth every
6 hours, beginning about 12 hours (+/- 2 hours) after you finish receiving methotrexate.
Each infusion will last about 1 hour. Leucovorin is given to lower the risk of side
effects such as mouth sores and kidney damage.
- On Days 1-3 of these cycles, you will receive Solu-Medrol (methylprednisolone) by vein
about every 12 hours. Each infusion will last about 2 hours.
- On Days 2 and 3 of these cycles, you will receive cytarabine by vein about every 12
hours. Each infusion will last about 2 hours.
- If the doctor thinks it is needed, on Days 1 and 8 for Cycles 2 and 4 only, you may also
receive rituximab by vein over several hours.
Additional Treatment during Intensive Chemotherapy:
- If your doctor thinks it is needed, on Day 2 of Cycles 1, 2, 3, and 4 only (+/- 2 days),
you will receive intrathecal methotrexate to help lower the risk of the disease coming
back in the fluid surrounding your brain.
- If your doctor thinks it is needed, on Day 7 of Cycles 1, 2, 3, and 4 only (+/- 2 days),
you will receive intrathecal cytarabine to help lower the risk of the disease coming
back in the fluid surrounding your brain.
- You will also receive either filgrastim every day or pegfilgrastim once after each
cycle. The drug will be given as injection just under your skin, until your white blood
cell counts have recovered. Your study doctor will tell you when this happens.
As long as the disease is responding to therapy and you have not had any intolerable side
effects, you will continue on intensive chemotherapy for up to 8 courses. At that point, you
will go on to the maintenance therapy phase.
Each maintenance cycle will be 28 days.
Maintenance chemotherapy will last for up to 2 years after you complete all 8 courses of
intensive chemotherapy. During maintenance chemotherapy:
- You will take mercaptopurine tablets by mouth 3 times a day.
- You will take methotrexate tablets by mouth once a week.
- On Day 1 of each cycle, you will receive vincristine by vein over about 30 minutes.
- On Days 1-5 of each cycle, you will take prednisone by mouth.
On Day 1 of Cycle 0:
- You will have a physical exam.
- Blood (about 1 tablespoon) will be drawn for routine tests. For the Day 1 tests, if you
have had any of these tests or procedures in the last 3 days, they may not need to be
On Days 8 and 15 of Cycle 0, you will have a physical exam.
Every week during Cycle 0, blood (about 1 tablespoon each time) will be drawn for routine
tests 3 times a week.
On Day 21 of every cycle, you will have a bone marrow aspiration and/or biopsy, to check the
status of the disease. Once your doctor believes the disease has shown enough response, this
will be done every 2-3 cycles at that point.
On Day 1 of Cycle 0 and every cycle after that, you will have a physical exam.
During the Intensive Chemotherapy cycles, blood (about 1 tablespoon each time) will be drawn
for routine tests every week. During Maintenance Chemotherapy cycles, these routine blood
samples will be drawn 1 time every month.
On Day 1 of every even-numbered cycle (Cycles 2, 4, 6, and so on), you will have an x-ray of
Length of Treatment:
You may receive the intensive chemotherapy for up to 8 cycles (up to 8 months) and then
maintenance therapy for up to 2 years. You may continue to take ruxolitinib or dasatinib
every day for as long as the doctor thinks it is in your best interest. 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.
Your participation on the study will be over after the follow-up visit.
You will have a follow-up visit 30 days after your last dose of the study drugs. At this
visit, you will be asked about any side effects you may be having. If you cannot make it to
the clinic for this visit, it can be done over the phone with a member of the study staff.
The phone call should last about 10 minutes.
This is an investigational study. Ruxolitinib is FDA approved and commercially available for
the treatment of myelofibrosis. Its use in this study is investigational. The study doctor
can explain how ruxolitinib is designed to work. Dasatinib is FDA approved and commercially
available for the treatment of CML and Philadelphia chromosome-positive ALL. All other drugs
used in this study are FDA approved and commercially available. Their use together in this
study is investigational. The study doctor can explain how the study drug(s) are designed to
You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.
Up to 92 participants will take part in this study. All will be enrolled at MD Anderson
1. Patients with previously treated B-cell ALL (relapsed and/or refractory after prior
2. Bone marrow involvement with >/= 5% lymphoblasts
3. Age >/= 10 years
4. Documented genetic lesion(s) known to confer susceptibility to inhibition by either
ruxolitinib or dasatinib or CRLF2 positivity by flow cytometry (for the Ruxolitinib
5. Eastern Cooperative Oncology Group (ECOG) performance status </= 2
6. Adequate organ function (total bilirubin < 2.0 mg/dL, SGPT or SGOT < 3 x upper limit
of normal [ULN], creatinine < 2 mg/dL)
7. Females of childbearing potential must have a negative serum or urine beta human
chorionic gonadotropin (Beta-hCG) pregnancy test result within 14 days prior to the
first dose of study drugs and must agree to use an effective contraception method
during the study and for 30 days following the last dose of study drug. Females of
non- childbearing potential are those who are postmenopausal greater than 1 year or
who have had a bilateral tubal ligation or hysterectomy. Appropriate methods of birth
control include the following: -- Any 2 of the following methods used together:
--Birth control implants, injections, or pills (except for progesterone only pills),
--Intrauterine device (IUD), --Vasectomy, --Tubal Ligation, --Barrier method (female
or male condom with spermicide, cervical cap with spermicide, diaphragm with
spermicide); --Male condom with spermicide and diaphragm; Male condom with spermicide
and cervical cap
8. (Continuation of #7) Unacceptable methods of birth control include using no birth
control, withdrawal, rhythm method, vaginal sponge, any barrier method that does not
use spermicide, progesterone only pills, and using male and female condoms at the same
9. 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
10. Patients or their legally authorized representative must provide written informed
1. Burkitt's Leukemia or Lymphoma, T-cell ALL or lymphoblastic lymphoma
2. Patients having undergone prior allogeneic stem cell transplant within 3 months or
having active graft versus host disease
3. Patient is pregnant or breastfeeding
4. Patients with uncontrolled active infections (Fever >/= 38 degree C, Septic shock)
5. Isolated extramedullary relapse (i.e. testicular, central nervous system)
6. Current or chronic hepatitis B or C infection, or known seropositivity for HIV
7. Concurrent chemotherapy (except intrathecal chemotherapy)
8. Major surgery within 4 weeks prior to first study dose
9. Systemic chemotherapy/radiotherapy/investigational therapy within 14 days (with the
exception of hydroxyurea and steroids) prior to starting therapy. For patients
receiving ALL maintenance with 6-mercaptopurine, methotrexate, vincristine, and
steroids - these agents should be discontinued at least 48 hours prior to start of
study drugs. For patients on oral targeted therapies (such as imatinib, dasatinib,
ponatinib), - these agents should be discontinued at least 48 hours prior to start of
10. Patients must have recovered from acute non hematologic toxicity (to </= grade 1) of
all previous therapy prior to enrollment
11. Known active central nervous system (CNS) leukemia, as defined by unequivocal
morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of
CNS-directed local treatment for active disease within the prior 28 days, symptomatic
CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction)
within 28 days. Patients may have history of CNS leukemic involvement if definitively
treated with prior therapy and no evidence of active disease (defined as >/= 2
consecutive spinal fluid assessments with no evidence of disease) at the time of
registration. Prophylactic intrathecal chemotherapy is not a criterion for exclusion.
12. Patients with active heart disease (NYHA class 3-4 as assessed by history and physical
examination, unstable angina/stroke/myocardial infarction within the last 6 months)
13. Patients with a cardiac ejection fraction (as measured by either Multi-gated
Acquisition (MUGA) scan or echocardiogram) < 40%. (Note: Patients who have had prior
anthracycline exposure of >250 mg/m2 may be eligible after discussion with the PI).
14. Second malignancy other than basal cell or squamous cell carcinoma of the skin or in
situ carcinoma of the cervix or the breast, unless they are successfully treated with
curative intent for more than 2 years before entering the study
15. Malabsorption syndrome or other conditions that preclude enteral route of
16. Patients requiring strong CYP3A4 inhibitors. (Complete list of inhibitors can be found
17. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that in the opinion of the investigator may increase the risk associated
with study participation or investigational product administration or may interfere
with the interpretation of study results and/or would make the patient inappropriate
for enrollment into this study.