Acute Myeloid Leukemia, Leukemia, Myelodysplastic Syndromes
Conditions
Brief summary
To compare an investigational oral form of the drug cladribine to the FDA approved form of the drug when it is given by vein (IV).
Detailed description
Objectives: * To compare the pharmacokinetic (PK) properties of oral cladribine (investigational product) and intravenous (IV) cladribine (reference standard drug) when administered to patients with hairy-cell leukemia (HCL) or T-cell prolymphocytic leukemia (T-PLL). Primary: * To identify a dose of oral cladribine that is bioequivalent to IV cladribine when the IV dose is administered via a 2-hour infusion to patients with HCL or T-PLL. Area under the curve (AUC) and maximum concentration (Cmax) will be measured and relative exposure of oral and IV cladribine will be assessed based on the geometric mean ratio and associated 90% confidence interval for dose-normalized AUCs and Cmax for oral-to-IV cladribine, as estimated from an appropriate linear mixed effects model. Secondary: * To assess the plasma PK of oral cladribine following single-dose and multiple-dose administration. * To identify a dose of oral cladribine that provides comparable exposure (AUC) to IV cladribine when the IV dose is administered via a 2-hour infusion to patients with HCL or T-PLL. * To assess the safety of oral cladribine in patients with HCL or T PLL. No formal efficacy evaluations will be performed in this study. All patients will be observed for complete remission (CR), complete remission without minimal residual disease (MRD), partial response (PR), progressive disease (PD) or stable disease (SD) at the end of the study, although response is not a study endpoint.
Interventions
DRUGCladribine
Given by PO and Given by IV (vein)
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Study participants must meet the following inclusion criteria 1. Patients, both men and women of all races and ethnic groups, aged ≥ 18 years are eligible for enrollment. 2. Provision of written informed consent prior to any study related procedures. 3. Patients with newly diagnosed or previously treated HCL who have indication for therapy and are candidates for cladribine therapy (all 3 cohorts). 4. Patients with previously treated T-cell prolymphocytic leukemia who have received at least one course of alemtuzumab-based treatment, who have documented indication for therapy and who are candidates for cladribine therapy (Cohort 1 and 2) only. 5. Adequate renal and hepatic organ function as indicated by the following laboratory values: 1. Creatinine clearance ≥ 60 mL/min 2. Serum total bilirubin ≤1.5×ULN (with the exception of patients with known Gilbert's syndrome: serum total bilirubin must be \<3×ULN in these patients) 3. Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤2.5×ULN or ≤5×ULN if due to leukemic involvement). 6. Adequate cardiac function with a left ventricular ejection fraction ≥45%. 7. Female patients are eligible to enter and participate in the study if they are of non-childbearing potential. Female patients of childbearing age must have a negative pregnancy test at screening and must not be breastfeeding and also agree to use at least 2 forms of effective birth control during the study treatment period and for at least 3 months after the last dose of investigational product. (See definitions in Appendix 2) 8. Male patients are eligible to enter and participate in the study if they agree to use effective methods of contraception during the study treatment period and for at least 3 months after the last dose of investigational product. (See definitions in Appendix 2)
Exclusion criteria
Study participants must not meet any of the following study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | through study completion; an average of 1 year |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFarhad Ravandi-Kashani, MD
M.D. Anderson Cancer Center
Outcome results
None listed