To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of nelarabine, etoposide and cyclophosphamide when given in combination to children with T-ALL and bone marrow relapse or T-LL.
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
For part I of the study: the recommended phase II dose of nelarabine in
combination with cyclophosphamide and etoposide
Secondary outcome
Secondary endpoints for this study include CR2 and CR2p as defined in section
10.1, and in addition:
* For T-ALL patients achieving CR2, ability to proceed to HSCT within 20 weeks
from study entry
* Minimal residual disease (MRD) levels at the end of each course of therapy
for T-ALL patients that attain CR2
Background summary
Nelarabine is one of the most recent medicine that is registered for pediatric
T-cell leukemia and lymphoma. Single agent data show clear anti-leukemic
activity. However, due to the risks of drug resistance mechanisms in the
treatment of hemato-oncology malignancies it is unusual to use nelarabine as
single agent therapy. In this study a treatment block is deveoped with
nelarabine, cyclophosphamide, and etoposide which can be seen as a T-cell
disease induction therapy. This is important because the cure rate of relapsed
T-cell ALL/NHL is very limited (<2-% overall survival at first relapse).
Study objective
To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities
(DLTs) of nelarabine, etoposide and cyclophosphamide when given in combination
to children with T-ALL and bone marrow relapse or T-LL.
Study design
Phase IB dose-escalation study, open label, non-randomized.
Intervention
The first part if the study will be a dose-escaltion study of nelarabine in
combination with etoposide and cyclophosphamide. Thsi will be followed by an
expansion cohort of 20 patients. Patients will be tretaed with 2 courses of
NECTAR cheotherapy in teh absence of progressive disease or DLTs.
Study burden and risks
Patients may suffer from regular side-effects such as known for intensive
chemotherapy given for hem malignancies in children, such as hematological
toxicity and febrile neutropenia, as well as the need for
Nelarabine is known for its potential neurological side-effects, and hence
patients may suffer from this. Other not yet known side-effects may occur when
the 3 drugs are combined
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Listed location countries
Age
Inclusion criteria
- Patients must be *1 and <18 years of age at the time of study enrollment (adpated for the NL)
- Patients must have T-cell ALL or T-cell lymphoblastic lymphoma (LL) in first relapse or must have failed primary induction chemotherapy
- ECOG 0-2 or Karnofsky * 50% for patients > 16 years of age; Lansky * 50% for patients *16 years of age. (See Appendix II for Performance Scales)
- Adequate renal function defined as serum creatinine * 1.5x upper limit of normal (ULN) for age. If the serum creatinine is above these values, the calculated creatinine clearance or radioisotope GFR must be * 70 mL/min/1.73m2.
- Total bilirubin * 1.5x ULN for age.
- If the total bilirubin is elevated, patient will still be eligible if the conjugated (direct) serum bilirubin * ULN for age.
- ALT * 5x ULN of normal for age.
- Adequate cardiac function defined as shortening fraction of * 27% by echocardiogram or ejection fraction * 45% by gated radionuclide study.
- Patients must have adequate pulmonary function
- All patients and/or their parents or legal guardians must sign a written informed consent.
Exclusion criteria
- Patients are excluded if they have CNS 3 disease
- Patients with Down syndrome are excluded.
- Patients with pre-existing Grade 2 (or greater) peripheral motor or sensory neurotoxicity per the CTCAE 3.0 as determined by the treating physician or a neurologist.
- Patients with a history of prior veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) or findings consistent with a diagnosis of VOD/SOS
- Patients are excluded if they have had
Previous hematopoietic stem cell transplantation;
Patients with a prior seizure disorder requiring anti-convulsants
- Patients are excluded if they have:
Positive blood culture within 48 hours of study enrollment;
Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection
- Plan to administer non-protocol chemotherapy, radiation therapy, immunotherapy, or any other investigational agents during the study period.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005923-42-NL |
| ClinicalTrials.gov | NCT00981799 |
| CCMO | NL37310.078.13 |