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

Phase 1

Conditions: T-cell or B-cell precursor (BCP) acute lymphoblastic leukaemia (T-ALL or BCP-ALL) or T-cell Non Hodgkin’s lymphoma (T-NHL)
MedDRA version: 9.1Level: LLTClassification code 10000844Term: Acute lymphoblastic leukaemia
MedDRA version: 9.1Level: HLGTClassification code 10025321Term: Lymphomas non-Hodgkin's T-cell

Registration Number: EUCTR2008-002219-42-FR

Lead Sponsor: Mundipharma Research Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 28

Inclusion Criteria

Subjects who are to be included in the study, are those who meet all of the following criteria:
1. Males and females aged = 2 years to = 18 years

2. Males and females = 13 kg

3. Unequivocal histological diagnosis of T-ALL, BCP-ALL or T-NHL (World Health
Organisation [WHO] classification) at initial diagnosis

4. T-ALL or T-NHL subjects:
a. 1st relapse after HSCT, or
b. =2 relapses, or
c. newly diagnosed subjects who are refractory to 1 standard induction
chemotherapy regimen, or
d. 1st relapse subjects who are refractory to 1 standard induction chemotherapy
regimen

BCP-ALL subjects:
a. = 2 relapses, or
b. newly diagnosed subjects who are refractory to 2 standard induction chemotherapy regimens, or
c. 1st relapse subjects who are refractory to 2 standard induction chemotherapy
regimens

Note: Relapse is defined as = 25% marrow blasts or reappearance of any nodal lesion(s) after documented complete response (CR).

Two regimens can be defined as either two different treatment regimens or the same
treatment regimen given to a subject who has relapsed after a durable response to the first treatment. A previous regimen can include a HSCT.

5. KPS or LPS (as appropriate for subject’s age) scores =60

6. Anticipated life expectancy of at least 6 weeks

7. Adequate kidney and liver function in the opinion of the Investigator and the Medical Monitor e.g. creatinine levels = 2.0 times upper limit of normal, 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

8. Female subjects of childbearing potential (i.e. have reached the age of menarche) must have a negative 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. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (hormonal), sexual abstinence or vasectomised partner

9. 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

10. Signed informed consent form and assent if appropriate according to local laws and regulations prior to start of any study specific procedures
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects who are to be excluded from the study are those who meet any of the following criteria:

1. Subjects with clinical evidence of active symptomatic CNS disease or isolated CNS
disease

2. Prior treatment with any antileukaemic 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. Corticosteroid use will not be excluded

3. Concurrent treatment with other anticancer agents (with the exception of CNS therapy,

4. Subjects with a history of HIV and/or HTLV-1 infection
Note: HIV and HTLV-1 testing will be performed at the Screening Visit for subjects who have not been tested within 3 months of screening. Results for HIV and HTLV-1 infection do not need to be available prior to initiation of treatment due to the aggressive nature of the disease. Subjects with a positive result will be evaluated on a case by case basis.

5. Subjects with known active HBV, HCV, CMV and/or EBV infection
Note: HBV, HCV, CMV and EBV testing will be performed at the Screening Visit for
subjects who have not been tested within 3 months of screening. Results for HBV, HCV, CMV and EBV do not need to be available prior to initiation of treatment due to the aggressive nature of the disease. Subjects with active disease will be evaluated on a case by case basis.

6. Subjects with active serious infection

7. Females who are pregnant (positive ß-hCG test) or lactating

8. Lack of full recovery from adverse drug reactions due to prior therapy, independent of when that therapy was given

9. 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

10. Any history of hypersensitivity or intolerance to any component of the study medication

11. Subjects who have received an investigational medicinal product in a clinical study 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

12. Previous enrolment in this clinical study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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