Ruxolitinib in Treating Patients with Chronic Myelomonocytic Leukemia

Status: Active

Description

This phase II trial studies how well ruxolitinib works in treating patients with chronic myelomonocytic leukemia. Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

Inclusion Criteria

  • Confirmed diagnosis of CMML using the World Health Organization (WHO) classification.
  • Must be able to adhere to the study visit schedule and other protocol requirements.
  • Patients must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for histopathological analysis and standard cytogenetic analysis during the screening procedure.
  • An Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1, or 2 is required.
  • Women of childbearing potential must have a negative pregnancy test at time of screening and baseline visits and agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, partner’s vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap).
  • Must understand and voluntarily sign an informed consent form.
  • Must have a life expectancy of greater than 3 months at time of screening.
  • Must have symptomatic splenomegaly and/or a Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF) Total Symptom Score (TSS) > 17.

Exclusion Criteria

  • Platelet count of less than 35,000/uL.
  • Absolute neutrophil count (ANC) of less than 250 cells/uL.
  • Serum creatinine >= 2.0.
  • Serum total bilirubin > 1.5 x upper limit of normal (ULN).
  • Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of CMML within 28 days of the first day of study drug treatment.
  • Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study.
  • Concurrent use of granulocyte-macrophage colony-stimulating factor (GM-CSF). Granulocyte colony-stimulating factor (G-CSF) could be used for the short-term management of neutropenic infection. Stable doses of erythropoietin stimulating agents that were started > 8 weeks from first ruxolitinib dose or corticosteroids that were being administered prior to screening are allowed.
  • Uncontrolled current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • History of metastatic malignancy in the preceding 2 years.
  • Pregnant women are excluded from this study because ruxolitinib has not been studied in pregnant patients. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib, breastfeeding should be discontinued if the mother is treated with ruxolitinib.

Locations & Contacts

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Eric Padron
Phone: 813-745-8264
Email: Eric.Padron@moffitt.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine overall response rates as measured by the international working myelodysplastic/myeloproliferative neoplasm (MDS/MPN) group criteria.

SECONDARY OBJECTIVES:

I. To determine the time to acute myeloid leukemia (AML) transformation of patients on ruxolitinib.

II. To determine the median overall survival.

III. To determine the duration of response achieved as in secondary endpoint one.

IV. To determine the change in symptom score from baseline to week 16.

V. To determine the change in spleen volume at 16 weeks.

VI. To determine if a correlation exist between the presence of the known recurrent mutations (JAK2, c-CBL, N-RAS, K-RAS, RUNX-1, TET2, SRSF2, EZH2, ASXL1, and DNMT3a) and response to ruxolitinib.

VII. To determine if a correlation exists between inflammatory cytokine secretion in the peripheral blood and response to ruxolitinib in chronic myelomonocytic (CMML) patients.

OUTLINE:

Patients receive ruxolitinib orally (PO) twice daily (BID) for 4 weeks. Treatment repeats every 4 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly up to week 48 and then every 6 months for 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Moffitt Cancer Center

Principal Investigator
Eric Padron

Trial IDs

Primary ID MCC-19727
Secondary IDs NCI-2019-04592
Clinicaltrials.gov ID NCT03722407