Description:
This phase I/II trial studies the side effects and best dose of ruxolitinib phosphate when
given together with decitabine and to see how well they work in treating patients with acute
myeloid leukemia that has come back or is not responding to treatment, or has developed from
a type of bone marrow diseases called myeloproliferative neoplasms. Ruxolitinib phosphate may
stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs
used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer
cells, either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving ruxolitinib phosphate together with decitabine may be an effective
treatment for acute myeloid leukemia.
Title
- Brief Title: Ruxolitinib Phosphate and Decitabine in Treating Patients With Relapsed or Refractory or Post Myeloproliferative Acute Myeloid Leukemia
- Official Title: Phase I/II Study of Ruxolitinib Plus Decitabine in Patients With Post Myeloproliferative Neoplasm - Acute Myeloid Leukemia (AML)
Clinical Trial IDs
- ORG STUDY ID:
2014-0344
- SECONDARY ID:
NCI-2014-02299
- SECONDARY ID:
2014-0344
- NCT ID:
NCT02257138
Conditions
- Blasts More Than 20 Percent of Bone Marrow Nucleated Cells
- Blasts More Than 20 Percent of Peripheral Blood White Cells
- Myelodysplastic/Myeloproliferative Neoplasm
- Recurrent Acute Myeloid Leukemia
- Refractory Acute Myeloid Leukemia
Interventions
Drug | Synonyms | Arms |
---|
Decitabine | 5-Aza-2'-deoxycytidine, Aza-TdC, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine | Treatment (ruxolitinib phosphate, decitabine) |
Ruxolitinib Phosphate | INCB-18424 Phosphate, Jakafi | Treatment (ruxolitinib phosphate, decitabine) |
Purpose
This phase I/II trial studies the side effects and best dose of ruxolitinib phosphate when
given together with decitabine and to see how well they work in treating patients with acute
myeloid leukemia that has come back or is not responding to treatment, or has developed from
a type of bone marrow diseases called myeloproliferative neoplasms. Ruxolitinib phosphate may
stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs
used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer
cells, either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving ruxolitinib phosphate together with decitabine may be an effective
treatment for acute myeloid leukemia.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the tolerability of the combination of decitabine and ruxolitinib phosphate
(ruxolitinib [DI]) in patients with leukemia. (Phase I) II. To determine the efficacy of
ruxolitinib in increasing and prolonging response induced by decitabine alone in patients
with post myeloproliferative neoplasm acute myeloid leukemia (AML) (post MPN-AML)
alternatively referred to as (myeloproliferative neoplasm - blast phase; MPN-BP). (Compared
to historical response rate with decitabine alone) (Phase II)
SECONDARY OBJECTIVES:
I. To compare whether there is a difference in response rate patients with post-MPN AML with
janus kinase 2 (JAK2) mutations and patients without JAK2 mutations.
OUTLINE: This is a phase I, dose-escalation study of ruxolitinib phosphate followed by a
phase II study.
Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-28 and
decitabine intravenously (IV) over 1-2 hours on days 1-5. Treatment repeats every 4-6 weeks
for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (ruxolitinib phosphate, decitabine) | Experimental | Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. | - Decitabine
- Ruxolitinib Phosphate
|
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of AML (World Health Organization [WHO] classification definition of >= to
20% blasts)
- In the phase I portion of the study all patients with relapsed or refractory AML are
eligible; for the Phase II portion of the study, patients must have AML progressing
from prior MPN (MPN-BP) or have myelodysplastic syndrome (MDS)/MPN with more than 20%
blasts; temporary prior measures to control blood counts, such as apheresis or Hydrea
are allowed; patients with newly diagnosed or previously treated disease are eligible
as long as prior therapy does not include hypomethylating agents; prior therapy for
ruxolitinib for MPN is allowed
- Serum biochemical values with the following limits unless considered due to leukemia:
- Creatinine =< 1.5 mg/dl
- Total bilirubin =< 1.5 mg/dL, unless increase is due to hemolysis or congenital
disorder
- Transaminases (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x upper limit of
normal (ULN)
- Ability to take oral medication
- Ability to understand and provide signed informed consent
- Performance status =< 3, unless directly related to disease process as determined by
the principal investigator
Exclusion Criteria:
- Any coexisting medical condition that in the judgment of the treating physician is
likely to interfere with study procedures or results including uncontrolled severe
infections, as well as uncontrolled cardiac disease, or other organ dysfunction;
patients with history of tuberculosis, human immunodeficiency virus (HIV) or hepatitis
B and C are excluded
- Nursing women, women of childbearing potential with positive blood pregnancy test
within 30 days of study start, or women of childbearing potential who are not willing
to maintain adequate contraception (such as birth control pills, intrauterine device
[IUD], diaphragm, abstinence, or condoms by their partner) over the entire course of
the study
- Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks
prior to study entry, excluding the placement of vascular access
- Active clinically serious and uncontrolled infection
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum tolerated dose of ruxolitinib phosphate, defined as the dose at which 0 or 1 of 6 patients experience dose-limiting toxicity (Phase I) |
Time Frame: | Up to 6 weeks |
Safety Issue: | |
Description: | Descriptive summaries will be provided for all patients for each safety parameter by course, grade, and relationship to treatment. |
Secondary Outcome Measures
Measure: | Proportion of patients without JAK2 mutations and any difference in response rate |
Time Frame: | Baseline |
Safety Issue: | |
Description: | The association between response and patient and disease characteristics will be examined by two-sample t-test (or Wilcoxon rank-sum test) or chi-square test. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | M.D. Anderson Cancer Center |
Last Updated
March 23, 2021