Ruxolitinib Phosphate and Decitabine in Treating Patients With Relapsed or Refractory or Post Myeloproliferative Acute Myeloid Leukemia

Phase 1

Completed

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: Decitabine
Other: Laboratory Biomarker Analysis
Drug: Ruxolitinib Phosphate

Registration Number: NCT02257138

Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment (ruxolitinib phosphate, decitabine) Ph1	Laboratory Biomarker Analysis	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.
Treatment (ruxolitinib phosphate, decitabine) Ph2	Laboratory Biomarker Analysis	Patients receive 50mg 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.
Treatment (ruxolitinib phosphate, decitabine) Ph2	Ruxolitinib Phosphate	Patients receive 50mg 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.
Treatment (ruxolitinib phosphate, decitabine) Ph1	Ruxolitinib Phosphate	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.
Treatment (ruxolitinib phosphate, decitabine) Ph1	Decitabine	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.
Treatment (ruxolitinib phosphate, decitabine) Ph2	Decitabine	Patients receive 50mg 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.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose of Ruxolitinib Phosphate (Phase I)	Up to 6 weeks	Maximum tolerated dose (MTD) is defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) is less than or equal to 17% (1 out of 6).
Number of Participants With a Response (Complete Response [CR] + CR With Incomplete Blood Count Recovery) (Phase 2)	Up to 6 years	Complete Response (CR) is defined as - The participant must be free of all symptoms related to leukemia and have an absolute neutrophil count \>/= 1 z 10\^9/L, no need for red blood cell transfusion, platelet count\>/+ 100 x 10\^9/L, and normal marrow differential (\</= 5 % blasts) in a normo- or hypercellular marrow. Complete Response with incomplete blood count recovery (CRi) is defined as - Same as CR but incomplete count recovery.
Number of Participants With Post-MPN Acute Myeloid Leukemia (AML) With JAK2 Mutations (Phase 2)	Baseline	JAK2 mutations were assessed with the baseline Bone Marrow or Peripheral Blood.

Secondary Outcome Measures

Name	Time	Method
Number of JAK2 Positive+ and JAK2 Negative- Participants With a Response (Phase 2)	up to 6 years	JAK2 mutations were assessed with the baseline Bone Marrow or Peripheral Blood. Complete Response (CR) is defined as - The participant must be free of all symptoms related to leukemia and have an absolute neutrophil count \>/= 1 z 10\^9/L, no need for red blood cell transfusion, platelet count\>/+ 100 x 10\^9/L, and normal marrow differential (\</= 5 % blasts) in a normo- or hypercellular marrow. Complete Response with incomplete blood count recovery (CRi) is defined as - Same as CR but incomplete count recovery.