MCC19727: A Sequential TwoStage Dose Escalation Study to Evaluate the Safety and Efficacy of Ruxolitinib for the treatment of Chronic Myelomonocytic Leukemia (CMML): A Phase 2 Expansion.
Details
Status
Open: Currently recruiting participants.
Closed: Recruitment either has not started or has paused or completed.
Study Type
Interventional (clinical trials): Test treatments.
Observational: Conduct surveys and interviews, study medical records and otherwise observe people or groups over time.
Interventional
Study Phase
Each study phase tests different aspects of the medication or treatment:
- Phase I: safety and dosing
- Phase II: effectiveness and side effects
- Phase III: efficacy compared to standard treatments
- Phase IV: long-term safety after approval for use
II
Location(s)
Johns Hopkins study sites. Additional study locations may be found on ClinicalTrials.gov.
The Johns Hopkins Hospital
1800 Orleans St Baltimore, MD 21287
Keywords
Contact Us
(410) 955-8964Brief Summary
Treatment will be administered on an outpatient basis. Reported adverse events and potential risks are described in Section 11. Appropriate dose modifications for ruxolitinib are described in Section 10. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's CMML. Ruxolitinib will be supplied by INCYTE as 5mg tablets. Ruxolitinib will be self-administered as a twice-daily oral dose for a continuous treatment cycle. Ruxolitinib tablets will be taken approximately 12 hours apart (morning and night). Patients will not take the morning dose of ruxolitinib at the first regularly scheduled visit. Drug will be administered in the clinic in order to obtain adequate biomarker assessment. On all other days corresponding to study visits, patients will take the morning dose of study drug prior to the visit, and will note on the subject reminder card the time that medications were taken. Patients will also be instructed to take ruxolitinib without respect to food, as previous data demonstrate no change in drug kinetics or absorption. All patients will be given 40 mg/day divided in equal BID doses. A maximum of 29 patients will be treated at the MTD identified in phase I of 20mg BID. See study calendar for assessment on study.
Eligibility
Inclusion Criteria:
- Confirmed diagnosis of Chronic Myelomonocytic Leukemia (CMML)using the World Health Organization (WHO) classification.
- 18 years of age or older at the time of obtaining informed consent.
- Must be able to adhere to the study visit schedule and other protocol requirements.
- Participants must be able to provide adequate 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 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.
- 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 an Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score >17.
Exclusion Criteria:
- Any of the following lab abnormalities: Platelet count of less than 35,000/uL, Absolute Neutrophil Count (ANC) less than 250/uL, Serum Creatinine ≥ 2.0, Serum total bilirubin >1.5x 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.
- Prior history of metastatic malignancy in past 2 years
- 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 participants. 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.