Study of Nelarabine, Etoposide and Cyclophosphamide in pediatric patients with T-ALL Relapse

• Conditions: relapsed T-ALL, T-NHL; MedDRA version: 14.1Level: LLTClassification code 10024338Term: Leukemia lymphoblastic acuteSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: HLGTClassification code 10025321Term: Lymphomas non-Hodgkin's T-cellSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2011-005923-42-NL
• Lead Sponsor: TAC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07-25
• Last Update Posted: 14 December 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 36

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 36
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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main 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. ;Secondary Objective: Secondary endpoints for this study include CR2 and CR2p as defined in section 10.1, and in addition:<br>• For T-ALL patients achieving CR2, ability to proceed to HSCT within 20 weeks from study entry<br>• Minimal residual disease (MRD) levels at the end of each course of therapy for T-ALL patients that attain CR2 ;Primary end point(s): For part I of the study: the recommended phase II dose of nelarabine in combination with cyclophosphamide and etoposide;Timepoint(s) of evaluation of this end point: 24 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary endpoints for this study include CR2 and CR2p as defined in section 10.1, and in addition:<br>• For T-ALL patients achieving CR2, ability to proceed to HSCT within 20 weeks from study entry<br>• Minimal residual disease (MRD) levels at the end of each course of therapy for T-ALL patients that attain CR2 ;Timepoint(s) of evaluation of this end point: 12-20 weeks