A Phase I/II Pharmacokinetic Study of Intravenous and Oral Forodesine in Children With Relapsed or Refractory T-cell or B-cell Precursor Acute Lymphoblastic Leukaemia or T-cell Non-Hodgkin's Lymphoma.
Inclusion Criteria:
- Males and females aged ≥ 2 years to ≤18 years. ≥ 13 kg
- Female subjects of childbearing potential (i.e. have reached the age of menarche)
must have a negative serum or urine pregnancy test recorded prior to the first dose
of study medication, be non-lactating, and be willing to use adequate and highly
effective method of contraception throughout the study and for one month after the
last dose of study medication, if sexually active.
- Sexually active male subjects must be willing and able to use a barrier form of
contraception (i.e. condoms) or sexual abstinence throughout the study and for one
month after the last dose of study medication
- Unequivocal histological diagnosis of T-ALL, BCP-ALL or T-NHL (World Health
Organisation [WHO] classification) at initial diagnosis
- Relapse (³25% marrow blasts) or failure to respond after at least one standard
regimen for their disease for subjects with a T-cell malignancy who are ineligible
for other therapy of greater curative potential, or failure to respond after at least
two standard regimens for subjects with a B-cell precursor malignancy
- KPS or LPS (as appropriate for subject's age) scores ³60
- Anticipated life expectancy of at least 6 weeks
- Adequate kidney (creatinine levels ≤ 2.0 times upper limit of normal) and liver
function tests (aspartate aminotransferase [AST] and/or alanine aminotransferase
[ALT] ≤3 times upper limit of normal and total bilirubin ≤5 times upper limit of
normal)
- Signed ICF and assent if appropriate according to local laws and regulations prior to
start of any study specific procedures.
Exclusion criteria:
- Females who are pregnant (positive β-hCG test) or lactating
- Subjects with a history of HIV and/or HTLV-1
- Subjects with known active HBV, HCV, CMV and/or EBV infection
- Subjects with clinical evidence of active symptomatic CNS disease
- Subjects with active serious infection
- Prior treatment with any antileukemic agent, chemotherapy or leukophoresis treatment
within 7 days (within 4-5 days for 6-mercaptopurine (MP) and within 2 days for
low-dose methotrexate) prior to study entry
- Lack of full recovery from adverse drug reactions due to prior therapy, independent
of when that therapy was given
- Concurrent treatment with other anticancer agents (CNS prophylaxis e.g. intrathecal
methotrexate and corticosteroid use will not be excluded)
- Subjects who have chronic gastrointestinal disease or conditions that may hamper
compliance and/or absorption of the product; however, study drug administration via
nasogastric or gastrostomy tube is allowed
- Any history of hypersensitivity or intolerance to any component of the study
medication.
- Subjects who have received an investigational medicinal product within 30 days of
study entry (defined as the start of the Screening Period).
- Current participation in another clinical trial is not permitted unless the sole
purpose of the trial is for long term follow up/survival data.