Chronic Myelomonocytic Leukemia, Leukemia
Conditions
Keywords
CMML
Brief summary
This study is to find out if treating Chronic Myelomonocytic Leukemia (CMML) with a study drug (ruxolitinib) can improve outcomes of patients with CMML.
Interventions
DRUGRuxolitinib
Ruxolitinib 5 mg tablets, 4 per dose
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Incyte Corporation
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response | At week 16 | Number of participants achieving clinical benefit defined as hematologic improvement, complete remission, partial remission, or stable disease by the International Working Group Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) Criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Acute Myeloid Leukemia (AML) Transformation | Every 6 months after conclusion of treatment until end of study (40.3 months) | Time to AML transformation according to World Health Organization (WHO) Critieria |
| Overall Survival | Up to 2 years | Overall survival will be from first dose of study drug until failure or death from any cause. |
| Duration of Response | Up to 2 years | Duration of response measured using time to AML transformation according to WHO Critieria |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREric Padron, MD
H. Lee Moffitt Cancer Center and Research Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ruxolitinib All patients will be given their first dose of oral Ruxolitinib, 20 mg at first scheduled visit. After that dose and on all other days patients will self-administer oral Ruxolitinib at a dose of 40 mg daily divided into two equal doses approximately 12 hours apart. Patients will be treated for a total of 16 weeks. After treatment, patients will be followed monthly.
Ruxolitinib: Ruxolitinib 5 mg tablets, 4 per dose | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Ruxolitinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 25 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 29 |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 20 / 29 |
Outcome results
Primary
Overall Response
Number of participants achieving clinical benefit defined as hematologic improvement, complete remission, partial remission, or stable disease by the International Working Group Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) Criteria.
Time frame: At week 16
Population: Evaluable participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib | Overall Response | Partial Response | 3 Participants |
| Ruxolitinib | Overall Response | Marrow Response | 2 Participants |
| Ruxolitinib | Overall Response | Stable Disease | 20 Participants |
Secondary
Duration of Response
Duration of response measured using time to AML transformation according to WHO Critieria
Time frame: Up to 2 years
Population: Participants who achieved a clinical response by MDS.MPN IWG response criteria.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib | Duration of Response | 0 months |
Secondary
Overall Survival
Overall survival will be from first dose of study drug until failure or death from any cause.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib | Overall Survival | 23.6 months |
Secondary
Time to Acute Myeloid Leukemia (AML) Transformation
Time to AML transformation according to World Health Organization (WHO) Critieria
Time frame: Every 6 months after conclusion of treatment until end of study (40.3 months)
Population: Participants who had AML transformation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib | Time to Acute Myeloid Leukemia (AML) Transformation | 5.0 months |