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

November 29, 2023 updated by: M.D. Anderson Cancer Center

Phase I/II Study of Ruxolitinib Plus Decitabine in Patients With Post Myeloproliferative Neoplasm - Acute Myeloid Leukemia (AML)

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.

Study Overview

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

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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:
  • 5-Aza-2'-deoxycytidine
  • Dacogen
  • Decitabine for Injection
  • Deoxyazacytidine
  • Dezocitidine
  • Aza-TdC
Given PO
Other Names:
  • Jakafi
  • INCB-18424 Phosphate
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:
  • 5-Aza-2'-deoxycytidine
  • Dacogen
  • Decitabine for Injection
  • Deoxyazacytidine
  • Dezocitidine
  • Aza-TdC
Given PO
Other Names:
  • Jakafi
  • INCB-18424 Phosphate

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

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Farhad Ravandi-Kashani, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 12, 2015

Primary Completion (Actual)

March 19, 2021

Study Completion (Actual)

March 19, 2021

Study Registration Dates

First Submitted

September 26, 2014

First Submitted That Met QC Criteria

October 1, 2014

First Posted (Estimated)

October 6, 2014

Study Record Updates

Last Update Posted (Estimated)

December 4, 2023

Last Update Submitted That Met QC Criteria

November 29, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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