Clinical trial NCT01787487: Ruxolitinib Phosphate and Azacytidine in Treating Patients With Myelofibrosis or Myelodysplastic Syndrome/Myeloproliferative Neoplasm
Official title: Evaluation of Ruxolitinib and Azacytidine Combination as a Therapy for Patients With Myelofibrosis and Myelodysplastic Syndrome/ Myeloproliferative Neoplasm
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Myelofibrosis Transformation in Essential Thrombocythemia
Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
Primary Myelofibrosis
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-02-08
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate (complete remission, partial remission, clinical improvement) in patients with myelofibrosis
timeFrame: Up to 24 weeks
measure: Objective response rate (complete remission, partial remission, and hematologic improvement) in patients with myelodysplastic syndromes/myeloproliferative neoplasms
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: 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
timeFrame: Up to 30 days after completion of study treatment
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Naval Daver, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.