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

NCT01787487 | Completed Phase 2 FDA Drug

• 2 other identifiers: 2012-0737NCI-2013-00704
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Primary Myelofibrosis; Myelofibrosis Transformation in Essential Thrombocythemia; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase

Outcome Measures

Primary Outcomes (2)

• Objective response rate (complete remission, partial remission, clinical improvement) in patients with myelofibrosis

  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

  The method of Thall, Simon and Estey will be used for futility monitoring for this study.

  Up to 24 weeks

Secondary Outcomes (1)

• 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

  Up to 30 days after completion of study treatment

Study Arms (2)

Arm I (MF patients)

EXPERIMENTAL

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.

Drug: Azacitidine; Other: Laboratory Biomarker Analysis; Drug: Ruxolitinib Phosphate

Arm II (MDS/MPN patients)

EXPERIMENTAL

Patients with MDS/MPN receive ruxolitinib phosphate and azacytidine as in Arm I.

Drug: Azacitidine; Other: Laboratory Biomarker Analysis; Drug: Ruxolitinib Phosphate

Interventions

Azacitidine DRUG

Given SC or IV

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Arm I (MF patients); Arm II (MDS/MPN patients)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (MF patients); Arm II (MDS/MPN patients)

Ruxolitinib Phosphate DRUG

Given PO

Also known as: INCB-18424 Phosphate, Jakafi

Arm I (MF patients); Arm II (MDS/MPN patients)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Masarova L, Verstovsek S, Hidalgo-Lopez JE, Pemmaraju N, Bose P, Estrov Z, Jabbour EJ, Ravandi-Kashani F, Takahashi K, Cortes JE, Ning J, Ohanian M, Alvarado Y, Zhou L, Pierce S, Gergis R, Patel KP, Luthra R, Kadia TM, DiNardo CD, Borthakur G, Bhalla K, Garcia-Manero G, Bueso-Ramos CE, Kantarjian HM, Daver N. A phase 2 study of ruxolitinib in combination with azacitidine in patients with myelofibrosis. Blood. 2018 Oct 18;132(16):1664-1674. doi: 10.1182/blood-2018-04-846626. Epub 2018 Sep 5.

  PMID: 30185431 DERIVED

• Assi R, Kantarjian HM, Garcia-Manero G, Cortes JE, Pemmaraju N, Wang X, Nogueras-Gonzalez G, Jabbour E, Bose P, Kadia T, Dinardo CD, Patel K, Bueso-Ramos C, Zhou L, Pierce S, Gergis R, Tuttle C, Borthakur G, Estrov Z, Luthra R, Hidalgo-Lopez J, Verstovsek S, Daver N. A phase II trial of ruxolitinib in combination with azacytidine in myelodysplastic syndrome/myeloproliferative neoplasms. Am J Hematol. 2018 Feb;93(2):277-285. doi: 10.1002/ajh.24972. Epub 2017 Nov 27.

  PMID: 29134664 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis

Interventions

Azacitidine; ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Naval Daver, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2013
• First Posted: February 8, 2013
• Study Start: March 13, 2013
• Primary Completion: January 20, 2026
• Study Completion: January 20, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (1)