A Phase 1, Open-Label, Sequential Cross-over, Bioavailability/Bioequivalence Study to Compare the Pharmacokinetics of Oral Cladribine With the Reference Listed Drug, Intravenous Cladribine

Prior treatment

• Active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody at screening. Patients who are hepatitis C antibody positive will need to have a negative PCR result prior to enrollment. Those who are hepatitis C PCR positive will be excluded. Patients who are hepatitis B virus surface antigen positive or hepatitis B PCR positive will be excluded. Patients who are anti-HBc antibody positive and who are surface antigen negative will need to have a negative PCR result before enrollment.
• Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation.

Other illness

• Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, malabsorption, or psychiatric illness/social situations that would limit compliance with study requirements.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the compounds in the study.

Lab values

• Receipt of live or live-attenuated vaccines within 4-6 weeks preceding oral cladribine treatment, planned during cladribine treatment or after cladribine treatment until the participant's immune system is no longer weakened (e.g., white blood cell counts are within normal limits).
• Human immunodeficiency virus (HIV) positive with a viral load >400 copies/mL and a CD4+ T-cell count of <350 cells/µL or with a history of an acquired immunodeficiency syndrome (AIDS) opportunistic infection within the past 12 months.
• Patients with baseline QTc >470 msec will not be enrolled in Cohort 1. If QTc changes are observed in response to cladribine in Cohort 1, then the protocol will be amended to exclude patients with baseline QTc >470 msec from Cohorts 2 and 3, as well

Other

• Study participants must not meet any of the following study exclusion criteria:
• Legal incapacity or limited legal capacity.
• Patients unwilling to comply with protocol requirements related to the assigned cohort.

• Study participants must meet the following inclusion criteria
• Patients, both men and women of all races and ethnic groups, aged ≥ 18 years are eligible for enrollment.
• Provision of written informed consent prior to any study related procedures.
• Patients with newly diagnosed or previously treated HCL who have indication for therapy and are candidates for cladribine therapy (all 3 cohorts).
• 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.
• Adequate renal and hepatic organ function as indicated by the following laboratory values:
  • Creatinine clearance ≥ 60 mL/min
  • 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)
  • Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤2.5×ULN or ≤5×ULN if due to leukemic involvement).
• Adequate cardiac function with a left ventricular ejection fraction ≥45%.
• 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)
• 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)