Clinical trial NCT01251965: Phase l/II Study of Ruxolitinib for Acute Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Leukemia
Keywords: Relapsed Acute Leukemia
Acute myeloid leukemia
AML
Acute lymphocytic leukemia
ALL
Ruxolitinib
Jakafi
INC424
INCB018424
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
First posted: 2010-12-02
Enrollment: 27
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Phase I is a standard 3+3 design and will be used to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and no formal evaluation of efficacy (response rate will be implemented. Patients in Phase I part who were treated at the MTD will be included toward patients assessed for response in the phase II stage.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to find the highest tolerable dose of ruxolitinib that can be given to patients with acute leukemia and to learn if the study drug can help control the disease. The safety of the drug will also be studied.

Detailed description: 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.

Eligibility criteria: 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 Alanine Aminotransferase (ALT) (SGOT) and/or Aspartate Aminotransferase (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. Eastern Cooperative Oncology Group (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 cytochrome P450 3A4 (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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: End of first 28 day cycle for toxicity
measure: Maximum Tolerated Dose (MTD) of Ruxolitinib
timeFrame: End of first 28 day cycle
Secondary outcomes:
measure: Participants With a Response
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Srdan Verstovsek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pemmaraju N, Kantarjian H, Kadia T, Cortes J, Borthakur G, Newberry K, Garcia-Manero G, Ravandi F, Jabbour E, Dellasala S, Pierce S, Verstovsek S. A phase I/II study of the Janus kinase (JAK)1 and 2 inhibitor ruxolitinib in patients with relapsed or refractory acute myeloid leukemia. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):171-6. doi: 10.1016/j.clml.2014.08.003. Epub 2014 Sep 17.