Clinical Trial 17259
A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML)
The purpose of this study is to find out if treating Chronic Myelomonocytic Leukemia (CMML) with a study drug [ruxolitinib] can improve outcomes of patients with CMML. The first step of the study is to learn the dose of ruxolitinib that is tolerable (bearable). It has already been studied in a number of patients with different bone marrow diseases and is approved for the treatment of a disease called Myelofibrosis; however, it is not approved for treatment of CMML. It is given orally (by mouth). Most people tolerate it well but the tolerability has not been determined in patients with CMML. We will be testing different doses to determine how much of the medication people can tolerate (bear) before they develop side effects.
- 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 procedure
- 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
- Estimated creatinine clearance of <60 mL/min
- Serum total bilirubin >1.5 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
- 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.
1.To determine the safety and tolerability of ruxolitinib in CMML subjects at diagnosis or relapse. (phase I)
2.To determine overall best response rates as measured by the international working group criteria (2006). (phase II)
1.To determine the time to AML transformation of subjects on Ruxolitinib.
2.To determine the median overall survival.
3.To determine the duration of response.
4.To determine the change in symptom score from baseline to best response.
5.To determine the change in spleen length at 16 weeks
6.To determine the change in downstream targets of JAK2 on ruxolitinib.
7.To determine if the in vitro activity of ruxolitinib correlates to response rates.
8.To determine the known recurrent mutations in the CMML cohort studied and there clinical relevance in the context of ruxolitinib.
9.To determine non-V617F JAK2 mutations at end of study or progression and there clinical relevance in the context of ruxolitinib.