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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00981799




Registration number
NCT00981799
Ethics application status
Date submitted
9/09/2009
Date registered
22/09/2009
Date last updated
1/10/2020

Titles & IDs
Public title
Trial of Nelarabine, Etoposide and Cyclophosphamide in Relapsed T-cell ALL and T-cell LL
Scientific title
A Phase I Trial of NECTAR (Nelarabine, Etoposide and Cyclophosphamide in T-ALL Relapse): A Joint Study of TACL and POETIC
Secondary ID [1] 0 0
T2008-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed T-Cell Acute Lymphoblastic Leukemia 0 0
Relapsed T-Cell Lymphoblastic Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nelarabine
Treatment: Drugs - Etoposide
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Methotrexate
Treatment: Drugs - Filgrastim

Experimental: Nelarabine Dose Level 1 - The study will begin at Dose Level 1 at 480 mg/m2 Nelarabine (75% of single agent maximum tolerated dose) and 330 mg/m2 Cyclophospamide and will escalate to the next Dose Level if the maximum tolerated dose (MTD) is not exceeded. The first 3 patients will be enrolled into Dose Level 1. If 0/3 experiences dose limiting toxicity (DLT) at a given dose level, then the dose is escalated to the next higher level and 3 more patients are enrolled. If 1/3 experiences DLT at current dose, the up to 3 more patients are accrued at the same dose level. If 2 or more DLTs are observed in a 3-patient or 6-patient cohort at a given dose level, then the MTD has been exceeded, dose escalation will be stopped, and up to 3 additional patients will be enrolled at the next lower dose level (unless 6 patients have already been treated at that prior dose). If the MTD is exceeded at Dose Level 0, the study will be closed.

Experimental: Nelarabine Dose Level 2 - Patients in this arm will be administered Nelarabine at 650 mg/m2 (100% of single agent MTD) and 330 mg/m2 Cyclophosphamide.

Experimental: Nelarabine Dose Level 3 - Patients in this arm will be administered Nelarabine at 650 mg/m2 (100% of single agent MTD) and 400 mg/m2 Cyclophosphamide

Experimental: Nelarabine Dose Level 0 - Patients in this arm will be administered Nelarabine 325 mg/m2 (50% of single agent MTD) and 330 mg/2 Cyclophosphamide. Patients will only enter this arm if the MTD at Dose Level 1 has been exceeded. If the MTD is exceeded at Dose Level 0, the study will be closed.


Treatment: Drugs: Nelarabine
Dose will be assigned at study entry. Nelarabine will be given IV over 60 minutes (given at hours 0 to 1) on days 1 through 5.

Treatment: Drugs: Etoposide
100 mg/m2/day IV over 2 hours (given at hours 1 to 3) on days 1 through 5

Treatment: Drugs: Cyclophosphamide
Dose will be assigned at study entry, IV as a 30-60 minute infusion (given at hours 3 to 4) on days 1 through 5.

Treatment: Drugs: Methotrexate
Give between day 29 and 36 or when ANC>750 and PLTS>75,000 - whichever comes first (but not prior to day 22) at the dose defined by age below, ideally in conjunction with BM evaluation.
Given intrathecally at the dose defined by age below. 8 mg for patients age greater than or equal to 1, but <2 years of age 10 mg for patients age greater than or equal to 2, but <3 years of age 12 mg for patients greater than or equal to 3, but < 9 years of age 15 mg for patients greater than or equal to >9 years of age

Treatment: Drugs: Filgrastim
5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is > 1000/mm3 for two consecutive days.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To Determine the Presence of 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.
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
To Determine the Complete Remission Rate After 1 and 2 Courses of This Therapy in Children With T-ALL and Bone Marrow Relapse or T-LL.
Timepoint [1] 0 0
1-3 months

Eligibility
Key inclusion criteria
- Patients to be enrolled in the dose-escalation portion of this study must have T-cell
ALL or T-cell lymphoblastic lymphoma (LL) in first relapse or must have failed primary
induction chemotherapy (ie, never attained a complete remission following an initial
course of standard therapy for T-ALL or T-LL). Patients to be enrolled in the cohort
expansion portion of this study (ie, those treated at the recommended phase 2 dose)
must have T-cell ALL in first relapse or must have failed primary induction
chemotherapy (ie, never attained a complete remission following an initial course of
standard therapy for T-ALL). T-LL patients are not eligible for the cohort expansion
phase.

- Patients with T-cell ALL must have greater than 25% blasts in the bone marrow with or
without extramedullary disease.

- Patients with T-cell LL must have recurrent disease, documented by clinical or
radiographic criteria, as well as histologic verification of the malignancy at
original diagnosis. Patients with T-cell LL enrolled in the phase I dose-escalation
study are not required to have measurable disease; however, patients enrolled in the
phase II cohort expansion at the MTD must have measurable disease.

- Patients may have CNS 1 or CNS 2 disease but not CNS 3.

- ECOG 0-2 or Karnofsky = 50% for patients > 16 years of age; Lansky = 50% for patients
=16 years of age.

- Patients may be enrolled on study regardless of the timing of prior Intrathecal
therapy; however, they MAY NOT BEGIN TREATMENT ON THIS PROTOCOL UNTIL A MINIMUM OF 7
DAYS HAS ELAPSED SINCE PRIOR INTRATHECAL THERAPY.

- At least 6 weeks must have elapsed since administration of nitrosureas.

- At least 12 weeks must have elapsed since administration of craniospinal or hemipelvic
radiation.

- Female patients of childbearing potential must have a negative urine or serum
pregnancy test confirmed within 2 weeks prior to enrollment.

- Female patients with infants must agree not to breastfeed their infants while on this
study.

- Male and female patients of child-bearing potential must agree to use an effective
method of contraception approved by the investigator during the study and for a
minimum of 6 months after study treatment.

- 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.

- No evidence of dyspnea at rest

- No exercise intolerance

- A pulse oximetry = 94% at sea level (= 90% at altitude = 5000 feet) if there is
clinical indication for determination.

- Patients and/or their parents or legal guardians must be capable of understanding the
investigational nature, potential risks and benefits of the study. All patients and/or
their parents or legal guardians must sign a written informed consent.
Minimum age
1 Year
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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) or findings consistent
with a diagnosis of VOD, defined as: conjugated serum bilirubin >1.4 mg/dL AND
unexplained weight gain greater than 10% of baseline weight or ascites AND
hepatomegaly or right upper quadrant pain without another explanation, OR reversal of
portal vein flow on ultrasound, OR pathological confirmation of VOD on liver biopsy.

- Previous hematopoetic stem cell transplantation.

- Patients with a prior seizure disorder requiring anti-convulsant therapy are not
eligible to receive nelarabine. For the purposes of this study, this includes any
patient that has received anticonvulsant therapy to prevent/treat seizures in the
prior two years.

- 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, or immunotherapy
during the study period.

- Any significant concurrent disease, illness, psychiatric disorder or social issue that
would compromise patient safety or compliance, interfere with consent, study
participation, follow up, or interpretation of study results.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/07/2016
Sample size
Target
Accrual to date
Final
23
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [3] 0 0
Royal Children's Hospital, Melbourne - Melbourne
Recruitment hospital [4] 0 0
Sydney Children's Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
United States of America
State/province [20] 0 0
Wisconsin
Country [21] 0 0
Austria
State/province [21] 0 0
Vienna
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
Canada
State/province [23] 0 0
Quebec
Country [24] 0 0
Canada
State/province [24] 0 0
Vancouver
Country [25] 0 0
France
State/province [25] 0 0
Lille
Country [26] 0 0
Italy
State/province [26] 0 0
Rome
Country [27] 0 0
Netherlands
State/province [27] 0 0
Rotterdam

Funding & Sponsors
Primary sponsor type
Other
Name
Therapeutic Advances in Childhood Leukemia Consortium
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Novartis
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Nelarabine has shown significant activity in patients with T-cell malignancies. This study
will determine the safety and maximum tolerated dose of the combination of nelarabine,
cyclophosphamide and etoposide in patients with first bone marrow relapse of T-ALL, or first
relapse of T-LL.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00981799
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jim Whitlock, MD
Address 0 0
The Hospital for Sick Children
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00981799