- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02257138
Ruxolitinib Phosphate and Decitabine in Treating Patients With Relapsed or Refractory or Post Myeloproliferative Acute Myeloid Leukemia
Phase I/II Study of Ruxolitinib Plus Decitabine in Patients With Post Myeloproliferative Neoplasm - Acute Myeloid Leukemia (AML)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (ruxolitinib phosphate, decitabine) Ph1
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.
|
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
|
Experimental: Treatment (ruxolitinib phosphate, decitabine) Ph2
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.
|
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose of Ruxolitinib Phosphate (Phase I)
Time Frame: 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).
|
Up to 6 weeks
|
Number of Participants With a Response (Complete Response [CR] + CR With Incomplete Blood Count Recovery) (Phase 2)
Time Frame: 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.
|
Up to 6 years
|
Number of Participants With Post-MPN Acute Myeloid Leukemia (AML) With JAK2 Mutations (Phase 2)
Time Frame: Baseline
|
JAK2 mutations were assessed with the baseline Bone Marrow or Peripheral Blood.
|
Baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of JAK2 Positive+ and JAK2 Negative- Participants With a Response (Phase 2)
Time Frame: 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.
|
up to 6 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Farhad Ravandi-Kashani, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Bone Marrow Diseases
- Hematologic Diseases
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Decitabine
Other Study ID Numbers
- 2014-0344 (Other Identifier: M D Anderson Cancer Center)
- NCI-2014-02299 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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