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

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ClinicalTrials.gov Identifier: NCT02257138
Recruitment Status : Recruiting
First Posted : October 6, 2014
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
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 Drug: Decitabine Other: Laboratory Biomarker Analysis Drug: Ruxolitinib Phosphate Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Ruxolitinib Plus Decitabine in Patients With Post Myeloproliferative Neoplasm - Acute Myeloid Leukemia (AML)
Actual Study Start Date : February 12, 2015
Estimated Primary Completion Date : February 1, 2019
Estimated Study Completion Date : February 1, 2019


Arm Intervention/treatment
Experimental: Treatment (ruxolitinib phosphate, 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.
Drug: Decitabine
Given IV
Other Names:
  • 5-Aza-2'-deoxycytidine
  • Aza-TdC
  • Dacogen
  • Decitabine for Injection
  • Deoxyazacytidine
  • Dezocitidine

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Ruxolitinib Phosphate
Given PO
Other Names:
  • INCB-18424 Phosphate
  • Jakafi




Primary Outcome Measures :
  1. 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 ]
    Descriptive summaries will be provided for all patients for each safety parameter by course, grade, and relationship to treatment.

  2. Proportion of patients achieving overall response (complete response [CR] + CR with incomplete blood count recovery) as assessed by myeloproliferative neoplasm (MPN) criteria (Phase II) [ Time Frame: Up to 18 weeks (3 courses) ]
    Presented with 95% confidence intervals. 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.

  3. Proportion of patients with post-MPN acute myeloid leukemia (AML) with JAK2 mutations [ Time Frame: Baseline ]
    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.


Secondary Outcome Measures :
  1. Proportion of patients without JAK2 mutations and any difference in response rate [ Time Frame: Baseline ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02257138


Contacts
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Contact: Farhad Ravandi-Kashani 713-745-0394 fravandi@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Farhad Ravandi-Kashani    713-745-0394      
Principal Investigator: Farhad Ravandi-Kashani         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Farhad Ravandi-Kashani M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02257138     History of Changes
Other Study ID Numbers: 2014-0344
NCI-2014-02299 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0344 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: October 6, 2014    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors