Ruxolitinib Phosphate and Azacytidine in Treating Patients With Myelofibrosis or Myelodysplastic Syndrome/Myeloproliferative Neoplasm

April 15, 2024 updated by: M.D. Anderson Cancer Center

Evaluation of Ruxolitinib and Azacytidine Combination as a Therapy for Patients With Myelofibrosis and Myelodysplastic Syndrome/ Myeloproliferative Neoplasm

This phase II trial studies how well ruxolitinib phosphate and azacytidine work in treating patients with myelofibrosis or myelodysplastic syndrome/myeloproliferative neoplasm. 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 azacytidine, 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 and azacytidine may be an effective treatment for myelofibrosis or myelodysplastic syndrome/myeloproliferative neoplasm.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the efficacy of the combination of RUX (ruxolitinib phosphate) with AZA (azacytidine) in patients with myelofibrosis (MF) (primary myelofibrosis, post polycythemia vera myelofibrosis, or post essential thrombocythemia myelofibrosis [PMF, post- PV MF, or post - ET MF]) in achieving objective improvements in disease status.

II. To determine the efficacy of the combination of RUX + AZA in patients with myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (breakpoint cluster region [BCR]-c-abl oncogene 1, non-receptor tyrosine kinase [ABL1] negative: aCML), and myelodysplastic syndromes/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U), in achieving objective improvements in disease status.

SECONDARY OBJECTIVES:

I. To determine the safety of the RUX + AZA combination in patients with MF and MDS/MPN.

TERTIARY OBJECTIVES:

I. To explore time to response (TTR) and duration of response (DOR). II. To explore the effect of the combination on anemia and transfusion dependence in patients with MF and MDS/MPN.

III. To explore the impact of baseline mutational profile on International Working Group (IWG)-Myeloproliferative Neoplasms Research and Treatment (MRT) response and overall survival in patients with MF and MDS/MPN.

IV. To explore the impact of baseline anemia on overall survival in patients with MF and MDS/MPN.

OUTLINE: Patients are assigned to 1 of 2 treatment arms.

ARM I (MF): Patients with MF receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-28. Beginning course 4, patients also receive azacytidine subcutaneously (SC) or intravenously (IV) for 5 days. Treatment repeats every 28 days for 15 courses in the absence of disease progression or unacceptable toxicity.

ARM II (MDS/MPN): Patients with MDS/MPN receive ruxolitinib phosphate and azacytidine as in Arm I.

After completion of study treatment, patients are followed up for 30 days and up to 5 years.

Study Type

Interventional

Enrollment (Estimated)

125

Phase

  • Phase 2

Contacts and Locations

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

Study Contact

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • M D Anderson Cancer Center
        • Principal Investigator:
          • Naval Daver
        • Contact:
          • Naval Daver
          • Phone Number: 713-794-4392

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:

  • Patients with a diagnosis of primary myelofibrosis (PM), post polycythemia vera myelofibrosis (PPV MF), or post essential thrombocythemia myelofibrosis (PET MF) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate or high risk according to International Working Group (IWG-MRT) criteria
  • Patients with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) that require therapy
  • Understanding and voluntarily signing an Institutional Review Board (IRB)-approved informed consent form
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Direct bilirubin of =< 2 mg/dL
  • Serum glutamate pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN) or 5 x ULN if related to MF or MDS/MPN associated liver infiltration
  • If total bilirubin is =< 2, fractionation is not required for eligibility determination
  • Creatinine =< 2.5 mg/dL
  • Platelets >= 50 x 10^9/L
  • Absolute neutrophil count (ANC) >= 1.0 x 10^9/L

Exclusion Criteria:

  • For the MF and MDS/MPN-U arms (arms 1 & 2), use of any other standard drug (except hydroxyurea, anagrelide, growth factors, Revlimid, clofarabine, etc) or experimental drug or therapy within 14 days of starting study therapy
  • Patients previously treated with RUX or AZA (only applicable for the MF and MDS/MPN arms)
  • Any serious psychological condition or psychiatric illness that would prevent the subject from signing the informed consent document, in the investigator opinion
  • Pregnant or lactating females
  • Subjects of childbearing potential who are unwilling to take appropriate precautions (from screening through follow-up) to avoid becoming pregnant or fathering a child; females of non-childbearing potential are defined as women who a) are 55 years of age with history of amenorrhea for 1 year OR b) are surgically sterile for at least 3 months; for females of childbearing potential, or for males, pregnancy must be avoided by taking appropriate precautions; these precautions and the methods of contraception should be communicated to the subjects and their understanding confirmed
  • Any condition which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Known positive for human immunodeficiency virus (HIV) or with known active infectious hepatitis, type A, B or C
  • Patients with active malignancy of other type than required for this study, are not eligible with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast; patients with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (MF patients)
Patients with MF receive ruxolitinib phosphate PO BID on days 1-28. Beginning course 4, patients also receive azacytidine SC or IV for 5 days. Treatment repeats every 28 days for 15 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Azacitidine
Given SC or IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
Drug: Ruxolitinib Phosphate
Given PO
Other Names:
  • Jakafi
  • INCB-18424 Phosphate
Experimental: Arm II (MDS/MPN patients)
Patients with MDS/MPN receive ruxolitinib phosphate and azacytidine as in Arm I.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Azacitidine
Given SC or IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza
Drug: Ruxolitinib Phosphate
Given PO
Other Names:
  • Jakafi
  • INCB-18424 Phosphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (complete remission, partial remission, clinical improvement) in patients with myelofibrosis
Time Frame: Up to 24 weeks
The method of Thall, Simon and Estey will be used for futility monitoring for this study. The objective response rate will be estimated along with the Bayesian 95% credible interval.
Up to 24 weeks
Objective response rate (complete remission, partial remission, and hematologic improvement) in patients with myelodysplastic syndromes/myeloproliferative neoplasms
Time Frame: Up to 24 weeks
The method of Thall, Simon and Estey will be used for futility monitoring for this study.
Up to 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events defined as grade 3-4 clinically relevant non-hematologic toxicity or a serious adverse event that is felt to be drug related as assessed by the Common Terminology Criteria for Adverse Events version 4.0
Time Frame: Up to 30 days after completion of study treatment
The method of Thall, Simon and Estey will be used for toxicity monitoring for this study.
Up to 30 days after completion of study treatment

Collaborators and Investigators

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

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Naval Daver, 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.

General Publications

Helpful Links

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)

March 13, 2013

Primary Completion (Estimated)

April 30, 2025

Study Completion (Estimated)

April 30, 2025

Study Registration Dates

First Submitted

February 6, 2013

First Submitted That Met QC Criteria

February 6, 2013

First Posted (Estimated)

February 8, 2013

Study Record Updates

Last Update Posted (Actual)

April 16, 2024

Last Update Submitted That Met QC Criteria

April 15, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012-0737 (Other Identifier: M D Anderson Cancer Center)
  • NCI-2013-00704 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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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