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A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML)

Phase 1/Phase 2
18 Years
Open (Enrolling)
Myelomonocytic Leukemia

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Trial Information

A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML)

This is a phase 1/2, two-stage, sequential cohort dose escalation study. If dose escalation
is completed as planned, no more than 53 subjects are expected to enroll onto this study at
a rate of approximately 3 subjects every month. For the Phase 2 study the Simon's optimal
two-stage design will be employed to test the null hypothesis that response rate (RR) equals
to 10% versus the alternative that RR equals to 30%.

Demographic and clinical variables for the study patients will be summarized using
descriptive statistics (mean, standard deviation, median, inter-quartile range, range, and
frequency counts and percentages). Safety and efficacy data will be analyzed overall as well
as separately for each dose cohort when appropriate.

Inclusion Criteria:

- Confirmed diagnosis of CMML using the World Health Organization (WHO) classification

- Age >18 years at the time of obtaining informed consent

- Must be able to adhere to the study visit schedule and other protocol requirements

- Must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for
histopathological analysis and standard cytogenetic analysis during the screening

- An Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1, or 2

- 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

Exclusion Criteria:

- Platelet count of less than 35,000/uL

- Absolute Neutrophil Count (ANC) of less than 250 cells/uL

- Serum creatinine > 2 upper limit of normal (ULN)

- Serum aspartic transaminase(AST) or alanine transaminase(ALT) >2.5 x ULN

- Serum total bilirubin >2.5 x 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 subjects. 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.

- Patients who have participated in other interventional (treatment-related) clinical
trials within 30 days of enrollment are excluded.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The maximum tolerated dose (MTD) of ruxolitinib for the treatment of Myelomonocytic Leukemia (CMML)

Outcome Description:

Phase I - The MTD is defined as the highest dose where less than 33% of subjects experience a drug related predefined dose limited toxicity (DLT).

Outcome Time Frame:

17 weeks

Safety Issue:


Principal Investigator

Eric Padron, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

February 2013

Completion Date:

September 2017

Related Keywords:

  • Myelomonocytic Leukemia
  • Chronic Myelomonocytic Leukemia
  • CMML
  • Leukemia
  • Leukemia
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Myelomonocytic, Acute



H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612